After Assisted Reproductive Technology Treatment Research Articles

Effect of metformin and exenatide on pregnancy rate and pregnancy outcomes in overweight or obese infertility PCOS women: long-term follow-up of an RCT.

The majority of Polycystic ovary syndrome (PCOS) are overweight or obese with increased infertility and high risk of pregnancy complications. We aim to compare efficacy of metformin and exenatide on spontaneous pregnancy rate, overall pregnancy rate after assisted reproductive technology treatment (ART) and pregnancy outcomes in overweight or obese infertility PCOS. In this long-term follow-up study, 160 overweight or obese infertility Chinese PCOS were randomized to exenatide or metformin treatment for 12weeks. Afterward, all were treated with metformin alone until pregnancy confirmed and followed until delivery. If patients failed spontaneous pregnancy during the second 12weeks, ART could be offered until end of 64weeks. The primary outcome was spontaneous pregnancy rate. At week 24, 29.2% of women in exenatide group conceived spontaneously while 14.7% in metformin group (p = 0.03). At week 64, total pregnancy rates were 79.2% in exenatide group and 76% in metformin group without significant difference (p = 0.65). Between two groups, there was no significant difference of pregnancy outcomes (p > 0.05). A stepwise logistic regression showed that spontaneous pregnancy was positively associated with body weight reduction and HOMA-IR improvement in either group. In overweight or obese infertility Chinese PCOS, 12weeks pregestational exenatide treatment resulted in more spontaneous pregnancy likely due to greater weight reduction and improvement of insulin resistance compared with metformin treatment without obvious benefit on overall pregnancy rate after ART or pregnancy outcomes of successful conceived women. This clinical trial was registered at Chinese Clinical Trials Registry (ChiCTR-IIR-16008084) on 13/3/2016.

First-Trimester Serum Cytokine Profile in Pregnancies Conceived After Assisted Reproductive Technology (ART) With Subsequent Pregnancy-Induced Hypertension.

Pregnancy-induced hypertension (PIH) is one of the most common pregnancy complications that seriously affects the mother and fetus. The incidence of PIH is higher in pregnancies conceived after assisted reproductive technology (ART) than in spontaneous pregnancies; thus, exploring potential serum biomarkers before PIH onset is of great significance for effective early prediction and prevention of PIH in the ART population. Cytokines are involved in the inflammatory response and immune regulation, which play an essential role in the pathogenesis of PIH. A description of the cytokine profile in the first trimester of pregnancy could help identify new diagnostic tools and develop targeted therapies for PIH in the ART population. The concentrations of classical predictive markers for PIH and another 48 cytokines were measured in the first-trimester pregnancy serum samples from 33 PIH patients and 33 matched normotensive controls (NC), both of whom conceived after ART treatment. The measured values were compared and analyzed between NC and PIH, followed by comprehensive bioinformatic analysis and logistic regression analysis. There was no significant difference in classical predictive markers, including Activin A, PlGF, sFLT1 (VEGFR), and sFLT1/PlGF, between the PIH and NC groups (P > 0.05), while 29 cytokines were significantly lower in the PIH group than in the NC group (P < 0.05). Logistic regression analysis revealed that 17 cytokines (IL-2Rα, M-CSF, IL-6, IL-2, β-NGF, IL-7, IL-12 (p70), SCF, IL-10, IL-9, MIG, GM-CSF, LIF, IL-1α, MCP-3, IL-4, and HGF) in the first-trimester pregnancy serum were significantly negatively correlated with the subsequent onset of PIH. With the top 3 cytokines (IL-7, MIG, and SCF) of receiver operating characteristic (ROC) analysis, we constructed an efficient multifactor combined detection and prediction model for PIH in ART pregnancy. Classical early predictors for hypertensive disorder complicating pregnancy cannot distinguish PIH from their normal peers in ART pregnancy. In comparison, the description of the cytokine profile in the first trimester of pregnancy enables us to distinguish high-risk ART pregnancy for PIH, permitting enough time for PIH prevention therapy. The cytokine profile we described also provides immunological insight into the further mechanistic exploration of PIH.

O-084 Risk of breast cancer for women who give birth after conception by assisted reproductive technology versus natural conception - a Nordic cohort study

Abstract Study question Are women who give birth after assisted reproductive technology (ART) at higher risk of breast cancer than women who give birth after natural conception? Summary answer Risk of breast cancer was similar or lower for women who gave birth after ART-conception compared to women who gave birth after natural conception. What is known already Most studies indicate no increase in breast cancer risk after use of ART, but results have been conflicting and with limited confounder control. Interpretation of existing knowledge is further complicated by the well-established dual effect of pregnancy on breast cancer risk, with short-term increase in risk and long-term protection. The population of ART-treated women is still relatively young and further studies are needed to understand how fertility treatment, pregnancy and causes of infertility collectively influence breast cancer risk in women treated with ART. Study design, size, duration Cohort study based on data linkage between the Medical Birth Registries, ART Registries, Population and Cause of Death Registries in Denmark (1994-2014), Finland (1990-2014), Norway (1984-2015) and Sweden (1985-2015) and the Cancer Registries in each country (1958-2014, 1954-2014, 1953-2015, 1958-2015, respectively). We included 2,283,592 women who gave their first birth during the study period, at age ≥25 years. Among these, 111,781 women had at least one birth after ART conception. Participants/materials, setting, methods Women without prior cancer were followed from first birth to date of first cancer, death, emigration, or end of follow-up. We compared risk of breast cancer in Cox regression for women who ever gave birth after ART (time-dependent) vs women with birth(s) after natural conception only, using age as the time scale. We included age at first birth, parity (time-dependent), country and year of delivery as covariates. Sub-analyses included height, body mass index and smoking. Main results and the role of chance Women who gave birth after ART were on average 3 years older than women who gave birth after natural conception. Among women who gave birth after ART, 1,101 were diagnosed with breast cancer during a median follow-up of 8.8 years (incidence rate 101/100,000 person-years), compared to 26,984 cases during a median follow-up of 12.7 years (incidence rate 91/100,000 person-years) among women with naturally conceived pregnancies. Age-specific rates were similar. After covariate adjustment, risk was slightly lower for women with ART vs natural conception (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.87 - 0.99). Further adjustment for height, body mass index and smoking gave similar results. Age at first birth was not clearly associated with breast cancer risk for women with either conception method. Women with ART-conception in their first two pregnancies had lower risk (HR 0.83, 95% CI 0.70 - 0.98), whereas no clear differences were found for women with both conception methods, compared to women with two naturally conceived pregnancies. Associations according to ART indication (male, ovarian, other female and unexplained infertility) were consistent with the main findings, as were results for treatment type (IVF, ICSI, fresh and frozen transfer, and single or double embryo transfer). Limitations, reasons for caution We had no data on unsuccessful ART treatments, number or type of stimulation cycles. Because only women who gave birth were included, and because a large proportion of ART-treated women had unknown cause of infertility, we cannot exclude residual confounding from causes or severity of infertility. Wider implications of the findings Women with successful ART treatment had similar or slightly lower risk of breast cancer compared to women who gave birth after natural conception. Although this study could not completely rule out adverse effects of ART on breast cancer risk, we found no evidence to support strong adverse effects. Trial registration number Not applicable

Live-born children after assisted reproduction in women with type 1 diabetes and type 2 diabetes: a nationwide cohort study

Aims/hypothesisType 1 and type 2 diabetes are among the most prevalent chronic diseases in women in the fertile years and women with diabetes may experience several reproductive issues. We aimed to examine the chance of biochemical pregnancy, clinical pregnancy and live birth after assisted reproductive technology (ART) treatment in women with type 1 and type 2 diabetes and whether obesity per se influenced the results.MethodsThis nationwide register-based cohort study is based on the Danish ART Registry comprising 594 women with either type 1 diabetes or type 2 diabetes from 2006 to 2017.ResultsRelative to women without diabetes, the adjusted OR (95% CI) of a live birth per embryo transfer was 0.50 (0.36, 0.71) in women with type 2 diabetes and 1.10 (0.86, 1.41) in women with type 1 diabetes.Conclusions/interpretationOur data on the efficacy of ART treatment in women with type 1 and type 2 diabetes is the first in this field. When compared with women without diabetes, women with type 1 diabetes had an equivalent chance of a live birth per embryo transfer whereas women with type 2 diabetes had a reduced chance. The findings in women with type 2 diabetes did not seem to be driven by obesity per se as the same pattern was seen in both normal-weight and obese women.Graphical abstract

The demographics of assisted reproductive technology births in a Nordic country.

STUDY QUESTIONWhat are the socio-demographic characteristics of families in Norway who have children after assisted reproductive technology (ART), and have these characteristics changed over time?SUMMARY ANSWERParents who conceive through ART in Norway tend to be advantaged families, and their socio-demographic profile has not changed considerably over the period 1985–2014.WHAT IS KNOWN ALREADYA small number of studies show that couples who conceive through ART tend to be socio-economically advantaged.STUDY DESIGN, SIZE, DURATIONNorwegian Population Register, the Medical Birth Register and the national data bases were linked to study all live births in Norway between 1985 and 2014.PARTICIPANTS/MATERIALS, SETTING, METHODSThe sample consisted of 1 757 768 live births. Simple bivariate analyses were performed to describe the socio-demographic characteristics of parents who conceived through ART and changes in these characteristics over the time period 1985–2014. We used linear probability models to estimate the association between parental income and giving birth after ART from 2000 to 2014, before and after adjustment for maternal age at delivery, education and area of residence.MAIN RESULTS AND THE ROLE OF CHANCEParents conceiving through ART were more likely to be older, with the highest levels of income and education, and married. Their socio-demographic profiles did not change considerably during the period 1985–2014. In the unadjusted model, parents belonging to the top income quartile were 4.2 percentage points more likely (95% CI: 4.1 to 4.3) to have conceived through ART than parents who belonged to the bottom income quartile. Adjustment for maternal age only partially reduced the income disparities (for the top income quartile by 35% (β = 2.7 with 95% CI: 2.5 to 2.8)). Additional adjustment for maternal education, marital status and area of residence did not further attenuate the associations.LIMITATIONS, REASONS FOR CAUTIONThe data does not enable us to tell whether the lower numbers of children conceived through ART amongst more disadvantaged individuals is caused by lower success rates with ART treatment, lower demand of ART services or barriers faced in access to ART. The study focuses on Norway, a context characterised by high subsidisation of ART services.WIDER IMPLICATIONS OF THE FINDINGSEven though in Norway access to ART services is highly subsidised, the results highlight important and persisting social inequities in use of ART. The results also indicate that children born after ART grow up in resourceful environments, which will benefit their development and well-being.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by European Research Council agreement n. 803959 (to A.G.), by Economic and Social Research Council grant ES/M001660/1 and by the Research Council of Norway through its Centres of Excellence funding scheme, project number 262700. The authors have no conflict of interest to declare.TRIAL REGISTRATION NUMBERNot applicable.

Cumulative Live Birth Rates in Low Prognosis Patients According to the POSEIDON Criteria: An Analysis of 26,697 Cycles of in vitro Fertilization/Intracytoplasmic Sperm Injection.

Objective: The POSEIDON criteria are used to stratify patients with low prognosis after assisted reproductive technology (ART) treatment. Since its introduction, there has been no large study about the prognosis of the POSEIDON population. We used the POSEIDON criteria in Chinese women who underwent repeated ART treatment and analyzed the association between POSEIDON criteria and the cumulative live-birth rate (CLBR).Methods: This was a retrospective cohort study of 62,749 women (97,388 cycles) who underwent ART treatment at the Reproductive and Genetic Hospital of CITIC-XIANGYA between January 2014 and June 2017. Among them, 19,781 (31.52%) women fulfilled the POSEIDON criteria, including 26,697 cycles. The optimal and conservative CLBRs within a complete IVF/ICSI treatment cycle were calculated, as well as the CLBRs following repeated ovarian stimulation cycles.Results: In POSEIDON groups 1, 2, 3, and 4, the optimal and conservative CLBRs of three complete consecutive in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were 83.87 and 66.06%, 53.67 and 37.72%, 44.24 and 27.98%, and 14.20 and 9.68%, respectively. The POSEIDON stratification [group 2: odds ratio (OR) = 2.319, 95% confidence interval (CI): 2.131–2.525, P < 0.001; group 3: OR = 1.356, 95% CI: 1.005–1.828, P = 0.046; group 4: OR = 3.525, 95% CI: 2.774–4.479, P < 0.001; all vs. group 1] and ovarian stimulation protocol [gonadotropin-releasing hormone (GnRH) antagonist protocol: OR = 1.856, 95% CI: 1.640–2.100, P < 0.001; other protocols: OR = 1.651, 95% CI: 1.155–2.361, P = 0.006; both vs. long GnRH agonist protocol] were associated with live birth in the first stimulation cycle. For the second stimulation cycle, the POSEIDON stratification (except POSEIDON group 3) and ovarian stimulation protocol were associated with live birth. A change in ovarian stimulation protocol was not associated with an improvement in the live birth rate.Conclusions: More than 30% of women who undergo IVF/ICSI treatment may be classified as low prognosis. Different reproductive outcomes were observed among the four POSEIDON groups. The most optimal outcomes after three successive cycles of IVF/ICSI treatment were observed in groups 1, 2, and 3.

The Effects of Subcutaneous Administration of Granulocyte Colony-Stimulating Factor on Pregnancy Outcome After Assisted Reproductive Technology: Clinical Trial

Background: Granulocyte-colony stimulating factor (G-CSF) is an innovative therapy in reproductive medicine. Although its mechanisms of action have remained unknown, G-CSF seems to be effective in the case of recurrent abortion or implantation failure and thin endometrium. Objectives: This study was conducted to investigate whether subcutaneous administration of G-CSF has any effect on pregnancy outcome after assisted reproductive technology (ART). Methods: Fifty women with male infertility factors undergoing ART treatment were enrolled and stimulated with the standard long protocol. The G-CSF group of women received one dose of subcutaneous G-CSF (Filgrastim, 300 µg/1 mL) on the day of embryo transfer and again two days later while the placebo group received normal saline. Results: Seventeen patients had a positive β-human chorionic gonadotropin concentration after embryo transfer (8 and 9 in G-CSF and placebo groups, respectively) although the difference was not statistically significant. In addition, spontaneous abortion occurred in three patients (1 patient in the G-CSF group vs. 2 patients in the placebo group). Conclusion: Overall, although G-CSF failed to affect the endometrial thickness, as well as implantation, or clinical pregnancy rates, a lower prevalence of abortion in G-CSF group may be due to the positive effect of G-CSF administration on the endometrium as compared to the placebo group.

Health of Infants After ART-Treated, Subfertile, and Fertile Deliveries.

To assess the risk of adverse health outcomes for infants after assisted reproductive technology (ART)-treated and subfertile as compared with fertile deliveries. Live-born singleton infants ≥23 weeks' gestational age (GA) born in Massachusetts between July 1, 2004, and December 31, 2010, were analyzed by linking a clinical ART database with state vital records. χ2 tests were used to compare the outcomes of fertile (those without ART treatment or other indicators of infertility), subfertile (indicators of infertility, no ART), and ART-treated (linked to ART deliveries) mothers, stratified by GA. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated by using multivariate logistic regression within each GA stratum, controlling for maternal sociodemographic and health characteristics. Compared with infants of fertile mothers (n = 336 705), infants born to subfertile (n = 5043) or ART-treated (n = 8375) mothers were more likely to be preterm (aOR 1.39 [95% CI 1.26-1.54] and aOR 1.72 [95% CI 1.60-1.85], respectively) and have respiratory and gastrointestinal and/or nutritional conditions (aOR range: 1.12-1.18). When stratified by GA, infants of subfertile or ART-treated mothers were at greater risk for congenital malformations and infectious diseases as well as cardiovascular and respiratory conditions (aOR range: 1.30-2.61; 95% CI range: 1.02-4.59). Compared with infants born to subfertile mothers, infants born to ART-treated mothers were at lower risk for being small for GA and having congenital malformations and cardiovascular conditions and at higher risk for infectious disease conditions. Compared with infants born to fertile mothers, infants of subfertile and ART-treated mothers are at greater risk for adverse health outcomes at birth beyond prematurity. The occurrence and magnitude of these risks vary by GA and organ systems.

Effect of preconceptional orlistat treatment on in-vitro fertilization outcome in overweight/obese women: study protocol for a randomized controlled trial

BackgroundObese women have fewer oocytes retrieved, an increased cancelation rate, a higher miscarriage rate, and a lower live birth rate after assisted reproductive technology (ART) treatment compared with women with normal weight. Weight loss before ART treatment can significantly improve pregnancy rates and/or live births. An orlistat plus diet intervention could promote weight loss, but there is no evidence from randomized clinical trials evaluating the effect of orlistat preconceptional treatment on pregnancy outcome in overweight and obese women.Methods/designWe are conducting a multicenter, randomized placebo-controlled, double-blind clinical trial in overweight and obese women aged 20–40 years undergoing in-vitro fertilization and embryo transfer (IVF-ET) with or without intracytoplasmic sperm injection, to evaluate whether orlistat treatment for 1–3 months before IVF-ET can improve the live birth rate. The primary outcome is live birth.DiscussionThe results of this study will provide evidence for the effect of preconceptional orlistat treatment on IVF outcome in overweight/obese women.Trial registrationChinese Clinical Trial Registry, ChiCTR-IPR-17011629. Registered on 11 June 2017.

Inpatient hospitalizations in women with and without assisted reproductive technology live birth.

The aim of this study is to evaluate frequency of hospitalization before, during, and after assisted reproductive technology (ART) treatment by cycle outcome. Six thousand and one hundred thirty women residing in Massachusetts undergoing 17,135cycles of ART reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SARTCORS) from 2004 to 2011 were linked to hospital discharges and vital records. Women were grouped according to ART treatment cycle outcome as: no pregnancy (n=1840), one or more pregnancies but no live birth (n=968), or one or more singleton live births (n=3322). Hospital delivery discharges during 1998-2011 were categorized as occurring before, during, or after the ART treatment. The most prevalent ICD-9 codes for non-delivery hospital discharges were compared. Groups were compared using chi square test using SAS 9.3 software. The proportion of any hospitalization was 57.0, 58.3, and 91.3% for women with no pregnancy, no live birth, and ART singleton live birth, respectively; the proportion of non-delivery hospitalizations was 30.4, 31.0, and 28.3%, respectively. The non-ART delivery proportion after ART treatment did not differ by group (33.4, 36.2, and 36.9%, respectively, p=0.17). Most frequent non-delivery diagnoses (including fibroids, obesity, ectopic pregnancy, depression, and endometriosis) also did not differ by group. A secondary analysis limited to only women with no delivery discharges before the first ART cycle showed similar results. All groups had live birth deliveries during the study period, suggesting an important contribution of non-ART treatment or treatment-independent conception to overall delivery and live births. Hospitalizations not associated with delivery suggested similarity in morbidity for all ART patients regardless of success with ART treatment.

Do ART patients face higher C-section rates during their stage of delivery? A German monocenter experience.

The mode of delivery depends on multiple parameters. After assisted reproductive technology (ART), previous studies have shown elevated C-section rates but few studies differentiated between elective and emergency operations and different protocols of cryopreservation. Because these studies did not use multiparity as exclusion criteria which reduces confounding with previous pregnancies, aim of this study is to compare mode of delivery of different techniques of ART using data of primiparae only [1, 2]. Retrospective analysis of patient data treated at the university hospital of Luebeck in a period of 12 years. Patients were divided in different groups according to their way of conception: spontaneous conception and conception afterART. The group of ART was further divided into: (a) a group of fresh transferred embryos (IVF/ICSI), (b) vitrification and (c) slow freezing. Exclusion criteria were defined as: multiparity, delivery <24.+0p.m., incomplete data and treatment outside university of Luebeck. Main parameter of this study was mode of delivery which was divided into spontaneous delivery or C-section. C-sections were further differentiated into elective or emergency C-sections. The group of fresh transferred embryos and slow freezing showed higher risks for elective and emergency C-sections (elective C-sections odds ratio 2.0, CI 95% 1.6-2.6, emergency C-sections odds ratio 1.4, CI 95% 1.1-1.9). Moreover, all groups of ART show enhanced risk of significant perinatal bleeding. Patients after ART treatment suffer from higher C-section rates during their stage of delivery.

Association between serum folate and vitamin B-12 and outcomes of assisted reproductive technologies

Preconceptional folate and vitamin B-12 have been linked to beneficial reproductive outcomes in both natural pregnancies and those after assisted reproductive technology (ART) treatment. The objective of the study was to evaluate the associations of serum folate and vitamin B-12 with ART outcomes. This analysis included a random sample of 100 women (154 ART cycles) participating in a prospective cohort study [Environment and Reproductive Health (EARTH)] at the Massachusetts General Hospital Fertility Center (2007-2013). Serum folate and vitamin B-12 were measured in blood samples collected between days 3 and 9 of treatment. Generalized estimating equations with adjustment for age, BMI, and race were used to evaluate the association of serum folate and vitamin B-12 with ART outcomes. Women in the highest quartile of serum folate (>26.3 ng/mL) had 1.62 (95% CI: 0.99, 2.65) times the probability of live birth compared with women in the lowest quartile (<16.6 ng/mL). Women in the highest quartile of serum vitamin B-12 (>701 pg/mL) had 2.04 (95% CI: 1.14, 3.62) times the probability of live birth compared with women in the lowest quartile (<439 pg/mL). Suggestive evidence of an interaction was observed; women with serum folate and vitamin B-12 concentrations greater than the median had 1.92 (95% CI: 1.12, 3.29) times the probability of live birth compared with women with folate and vitamin B-12 concentrations less than or equal to the median. This translated into an adjusted difference in live birth rates of 26% (95% CI: 10%, 48%; P = 0.02). Higher serum concentrations of folate and vitamin B-12 before ART treatment were associated with higher live birth rates among a population exposed to folic acid fortification. This trial was registered at clinicaltrials.gov as NCT00011713.

Cancer in women after assisted reproductive technology

To evaluate the risk of cancer after assisted reproductive technology (ART) therapy. Longitudinal cohort study. Not applicable. New York, Texas, and Illinois residents between 2004 and 2009, treated with ART, comprising cycles of 113,226 women, including 53,859 women without prior ART treatment, who were linked to their respective state cancer registries and whose cycles were reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS). None. Diagnosis of cancer, as reported to the state cancer registry; standardized incidence ratios (SIR) and their 95% confidence intervals, comparing the observed to expected cancer cases based on age-specific cancer rates in the general population of each state. Among the cohort of women without prior ART therapy, hazard ratios (HR) and 95% confidence intervals (CI) were calculated for treatment parameters and reproductive history factors. The mean follow-up period was 4.87 years; among women without prior ART, 450 women developed 460 cancers. Women treated with ART had a statistically significantly lower risk for all cancers (for all women: SIR 0.78; CI, 0.73-0.83; women without prior ART: SIR 0.75; CI, 0.68-0.82), breast cancer, and all female genital cancers; a non-statistically-significant lower risk for endocrine and uterine cancer; and a non-statistically-significant higher risk for melanoma and ovarian cancer. Among women without prior ART, we found no statistically significant increased HR by parity, number of cycles, cumulative follicle-stimulating hormone dosage, or cycle outcome. Women initiating ART treatment have no greater risk for developing cancer after nearly 5 years of follow-up compared with the general population and with other women treated with ART.

Risk of preterm birth after blastocyst embryo transfer: a large population study using contemporary registry data from Australia and New Zealand

To investigate whether there is an increased risk of preterm birth with blastocyst transfer compared with cleavage-stage embryo transfer (ET) after assisted reproductive technology (ART). A retrospective, population-based study. Not applicable. A total of 50,788 infants conceived after ART treatment performed from 2009 to 2012. None. The rates of preterm birth, low birth weight (LBW), and small for gestational age (SGA) for 43,952 singleton and 3,418 twin deliveries after transfers of blastocyst or cleavage-stage embryos. Among singletons, there was no significant difference in the odds of preterm birth between blastocyst and cleavage-stage ET (9.1% compared with 9.3%, respectively, adjusted odds ratio 1.00, 95% confidence interval 0.94-1.08). Among twins, the crude rates of preterm birth were similar after blastocyst and cleavage-stage ETs (61.5% and 64.4%, respectively). However, after adjusting for potential confounders, blastocyst transfer was associated with a lower odds of preterm birth among twins (adjusted odds ratio 0.80, 95% confidence interval 0.70-0.93). There was no difference in risks of LBW and SGA between blastocyst and cleavage-stage ETs for both singletons and twins after adjusting for potential confounders. In contrast with the findings from a number of other studies, blastocyst culture in Australian and New Zealand is not associated with an increased risk of preterm, LBW, and SGA for singletons. Further studies are needed to assess longer-term outcomes of children born after ART treatment and possible biological or treatment factors related to adverse outcomes.

Are repeated assisted reproductive technology treatments and an unsuccessful outcome risk factors for unipolar depression in infertile women?

Previous studies have shown conflicting results as to whether unsuccessful medically assisted reproduction is a risk factor for depression among women. This study therefore investigated if women with no live birth after assisted reproductive technology (ART) treatment had a higher risk of unipolar depression compared with women with a live birth after ART treatment. The Danish National ART-Couple (DANAC) Cohort is a national register-based cohort study that consists of women who received ART treatment from 1 January 1994 to 30 September 2009, in Denmark (n = 41 050). Information on unipolar depression was obtained from the Danish Psychiatric Central Research Register. The analyses were conducted in Cox regression analysis. During the 308 494 person-years of follow up, 552 women were diagnosed with unipolar depression. A Cox proportional hazards model showed that women in ART treatment, with no live birth yet, had a lower risk of unipolar depression compared with women with a live birth. Women had the highest risk of unipolar depression 0-42 days after a live birth (adjusted hazard ratio 5.08, 95% CI 3.11-8.29) compared with women with no live birth. A lower, but still increased, risk of unipolar depression, was found in women 43 days to 1 year and >1 year after a live birth compared with women with no live birth yet. Motherhood is an important trigger of unipolar depression in women conceiving after ART treatment.

Risk of Chromosomal Abnormalities in Early Spontaneous Abortion after Assisted Reproductive Technology: A Meta-Analysis

BackgroundStudies on the risk of chromosomal abnormalities in early spontaneous abortion after assisted reproductive technology (ART) are relatively controversial and insufficient. Thus, to obtain a more precise evaluation of the risk of embryonic chromosomal abnormalities in first-trimester miscarriage after ART, we performed a meta-analysis of all available case–control studies relating to the cytogenetic analysis of chromosomal abnormalities in first-trimester miscarriage after ART.MethodsLiterature search in the electronic databases MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) based on the established strategy. Meta-regression, subgroup analysis, and Galbraith plots were conducted to explore the sources of heterogeneity.ResultsA total of 15 studies with 1,896 cases and 1,186 controls relevant to the risk of chromosomal abnormalities in first- trimester miscarriage after ART, and 8 studies with 601 cases and 602 controls evaluating frequency of chromosome anomaly for maternal age≥35 versus <35 were eligible for the meta-analysis. No statistical difference was found in risk of chromosomally abnormal miscarriage compared to natural conception and the different types of ART utilized, whereas the risk of fetal aneuploidy significantly increased with maternal age≥35 (OR 2.88, 95% CI: 1.74–4.77).ConclusionsART treatment does not present an increased risk for chromosomal abnormalities occurring in a first trimester miscarriage, but incidence of fetal aneuploidy could increase significantly with advancing maternal age.

Paternal body mass index is associated with decreased blastocyst development and reduced live birth rates following assisted reproductive technology

To determine the relationship between paternal body mass index (BMI), embryo development and pregnancy, and live birth outcomes after assisted reproductive technology (ART). Retrospective analysis of ART cycles. Major assisted reproduction center. Three hundred five couples undergoing ART in a private fertility clinic. No intervention was undertaken in patients involved in this study. Live birth outcomes and clinical pregnancy rates. No significant relationship between paternal BMI and early embryo development was found. However, increased paternal BMI was associated with decreased blastocyst development, clinical pregnancy rates and live birth outcomes. To our knowledge, this is the first report linking increased paternal BMI and clinical pregnancy and live birth rates after ART treatment. Further work to elucidate the mechanisms involved is required.

First‐trimester screening markers are altered in pregnancies conceived after IVF/ICSI

To determine the levels of first-trimester screening markers and to assess the false-positive rate for first-trimester combined screening for Down syndrome in a large national population of women pregnant after assisted reproductive technology (ART), in order to decide whether or not to correct risk calculation for mode of conception. A national prospective cohort study of 1000 pregnancies achieved after ART was compared with a control group of 2543 pregnancies conceived spontaneously. All women completed a first-trimester combined screening program. Risk calculation was performed retrospectively based on the screening parameters to avoid bias due to the use of different algorithms of risk calculation. In chromosomally normal pregnancies conceived after in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), the pregnancy-associated plasma protein-A multiples of the median value was significantly decreased when compared with that of pregnancies conceived spontaneously (0.78 and 0.79 vs. 0.98), while there was no difference in the group treated by frozen embryo replacement. There was no difference in the level of free beta-human chorionic gonadotropin between groups. The median nuchal translucency thickness was smaller in the overall ART group compared with controls. The false-positive rate of first-trimester combined screening in the overall ART group, adjusted for maternal age, was significantly higher when compared with controls (9.0% vs. 6.0%). It seems advisable to use a population of IVF/ICSI pregnancies to establish median curves for the first-trimester serum screening parameters and perhaps also for nuchal translucency thickness. However, care must be taken, as different ART treatment methods and aspects of medical history seem to alter the screening parameters in different ways.

Babies born after ART treatment cost more than non-ART babies: a cost analysis of inpatient birth-admission costs of singleton and multiple gestation pregnancies

Currently, about one-third of infants born after assisted reproductive technology (ART) worldwide are twins or triplets. This study compared the inpatient birth-admission costs of singleton and multiple gestation ART deliveries to non-ART deliveries. A cohort of 5005 mothers and 5886 infants conceived following ART treatment were compared to 245 249 mothers and 248 539 infants in the general population. Birth-admission costs were calculated using Australian Refined Diagnosis Related Groups and weighted national average costs (2003-2004 euro). ART infants were 4.4 times more likely to be low birthweight (LBW) compared with non-ART infants, translating into 89% higher birth-admission costs (euro2,832 and euro1,502, respectively). ART singletons were also more likely to be LBW compared with non-ART singletons, translating into 31% higher birth-admission costs (euro1,849 and euro1,415, respectively). After combining infant and maternal admission costs, the average cost of an ART singleton delivery was euro4,818 compared with euro13 890 for ART twins and euro54 294 for ART higher order multiples. Findings were not sensitive to changes in casemix. The poorer neonatal outcomes of ART singletons compared with non-ART singletons are significant enough to impact healthcare resource consumption. The high costs associated with ART multiple births add to the overwhelming clinical and economic evidence in support of single embryo transfer.

Patient dropout in an assisted reproductive technology program: implications for pregnancy rates

Objective: To study patient dropout and its impact on crude and cumulative pregnancy rates (PRs) after assisted reproductive technology (ART). Design: Retrospective cohort study. Setting: University hospital-based tertiary care fertility clinic. Patient(s): Two hundred two couples applying for their first ART treatment cycle. Main Outcome Measure(s): Drop-out rate and PR per cycle, cumulative drop-out rate and cumulative PR. Result(s): After three treatment cycles, the cumulative drop-out rate was 126 of 202 (62.4%); 13.9% (n = 28) was due to active censoring. Active censoring was shown to flatter cumulative PRs by life-table analysis. Conclusion: Dropout from ART is high, even when ART costs are covered by health cost insurance. Life-table analysis overestimates cumulative PRs in ART.