Including In Vitro Fertilization Research Articles

Association between adenomyosis and placenta accreta and mediation effect of assisted reproductive technology on the association: A nationwide observational study.

To investigate the association between adenomyosis and placenta accreta spectrum (PAS) and to evaluate the effect of assisted reproductive technology (ART) in mediating this association. We retrieved data for singleton women from the Japanese nationwide perinatal registry between 2013 and 2019, excluding women with a history of adenomyomectomy. To investigate the association between adenomyosis and PAS among women, we used a multivariable logistic regression model with multiple imputation for missing data. We evaluated mediation effect of ART including invitro fertilization and intracytoplasmic sperm injection on the association between adenomyosis and PAS using causal mediation analysis based on the counterfactual approach. Of 1 500 173 pregnant women, 1539 (0.10%) had adenomyosis. The number receiving ART was 489/1539 (31.8%) and 117 482/1 498 634 (7.8%) in women with and without adenomyosis, respectively. The proportion of women who developed PAS was 21/1539 (1.4%) in women with adenomyosis and 7530/1 498 634 (0.5%) in women without adenomyosis. Adenomyosis was significantly associated with PAS (odds ratio [OR] 1.95; 95% confidence interval [CI] 1.26-3.00; P = 0.002). Mediation analysis showed that OR of the total effect of adenomyosis on PAS was 1.98 (95% CI 1.13-3.04), OR of natural indirect effect (effect explained by ART) was 1.15 (95% CI 1.01-1.41), and OR of natural direct effect (effect unexplained by ART) was 1.72 (95% CI 0.86-2.82). The proportion mediated (natural indirect effect/total effect) was 26.5%. Adenomyosis was also significantly associated with PAS without previa (OR 1.96; 95% CI 1.23-3.13, P = 0.005). Adenomyosis was significantly associated with PAS. ART mediated 26.5% of the association between adenomyosis and PAS.

Is infertility more common among patients with multiple sclerosis? Implications to assisted reproductive techniques utilization

Research QuestionTo evaluate whether fertility is affected, and the usage of assisted reproductive treatment (ART), among women with multiple sclerosis (MS). DesignData regarding MS and ART usage among patients with multiple sclerosis was extracted from the Israeli HMO - Clalit Health Service database. Data regarding diagnosis and treatment of MS, cause of infertility and fertility treatments usage were collected for all female MS patients aged 18-45 between the years 2005-2020. Each MS patient was matched by age 1:10 with reference women from the general population. The prevalence of infertility was compared between the two groups. Univariate and multivariate statistical tests were used to analyze the association between MS and fertility treatments including in vitro fertilization (IVF) and controlled ovarian hyperstimulation (COH). ResultsDuring the study period, 1309 MS patients were compared to 13,090 controls from the general population matched for age. Mean age was 29 (±7.8 SD) years old. The overall prevalence of infertility was 15.4% (202/1309) among MS patients, similar to the general population 16.3% (2129/13090) p=0.939. The prevalence of both IVF and COH were similar among MS patients and matched controls from the general population (8.1% vs 7.2% p=0.427, 13.8% vs 14.3% p=0.624 accordingly). ConclusionsOur results show similar rate of infertility and fertility treatments among MS patients and the general population. The results of this study provide reassurance that fertility among women with MS do not differ from the general women population, and indicate no excessive assisted reproductive technology utilization.

Long-Term Effects of ART on the Health of the Offspring.

Assisted reproductive technologies (ART) significantly increase the chance of successful pregnancy and live birth in infertile couples. The different procedures for ART, including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), intrauterine insemination (IUI), and gamete intrafallopian tube transfer (GIFT), are widely used to overcome infertility-related problems. In spite of its inarguable usefulness, concerns about the health consequences of ART-conceived babies have been raised. There are reports about the association of ART with birth defects and health complications, e.g., malignancies, high blood pressure, generalized vascular functional disorders, asthma and metabolic disorders in later life. It has been suggested that hormonal treatment of the mother, and the artificial environment during the manipulation of gametes and embryos may cause genomic and epigenetic alterations and subsequent complications in the health status of ART-conceived babies. In the current study, we aimed to review the possible long-term consequences of different ART procedures on the subsequent health status of ART-conceived offspring, considering the confounding factors that might account for/contribute to the long-term consequences.

Predictors of Adverse Fetal Outcomes in Intrahepatic Cholestasis of Pregnancy (ICP): a Narrative Review.

Intrahepatic cholestasis of pregnancy (ICP) is a hepatic disorder in pregnancy linked with adverse fetal outcomes, which primarily manifests in the late second and third trimesters of pregnancy. This review aims to recapitulate the existing evidence on factors that can predict detrimental perinatal outcomes in pregnant women diagnosed with intrahepatic cholestasis of pregnancy. We searched PubMed, Web of Science, Cochrane Library, Scopus, Medline, and Embase databases and selected studies related to predictors of fetal outcome in intrahepatic cholestasis of pregnancy. Studies of the articles showed that predictors of an adverse fetal outcome include in vitro fertilization (IVF) pregnancy, multifetal pregnancy, biochemical markers, gestational age of ICP onset, presence of comorbidities (preeclampsia and gestational diabetes mellitus), maternal history of ICP, and hepatobiliary disease.Intrahepatic cholestasis of pregnancy (ICP) complicates the pregnancy. Hence, early assessment of low-risk and high-risk groups will help to administer definite management protocols and strategies to prevent adverse neonatal outcomes. Further research should concentrate on the number of conditions/factors and the predictive power of different factors to determine the most reliable predictors and biomarkers that can predict adverse fetal outcomes and improve the assessment of risk in pregnancy complicated with ICP.

Fertility Challenges in Asthmatic Women: Examining the Complexities of Pregnancy Loss, Infertility, and Assisted Reproductive Technologies.

Asthma is a prevalent chronic respiratory condition affecting a significant portion of women of reproductive age. While the impact of asthma on general health and well-being has been extensively studied, its association with fertility challenges in women remains an area of growing concern. This review article explores the complexities surrounding fertility challenges in asthmatic women, specifically focusing on pregnancy loss, infertility, and the utilization of assisted reproductive technologies (ARTs). Various factors contribute to the heightened risk of pregnancy loss in asthmatic women, including the systemic inflammation associated with asthma, suboptimal asthma control, medication usage, and comorbidities. The review highlights the need for multidisciplinary management approaches to optimize asthma control before and during pregnancy, reducing the risk of adverse pregnancy outcomes. Furthermore, the review investigates the potential impact of asthma on female fertility and the underlying mechanisms involved. Asthma-related factors, such as chronic inflammation, altered hormonal balance, and medication effects, may disrupt the delicate reproductive processes, leading to infertility. It emphasizes the importance of comprehensive fertility evaluations and personalized treatment strategies for asthmatic women experiencing difficulties conceiving. Additionally, the article explores the utilization of ARTs, including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), in asthmatic women. It discusses the safety considerations and potential challenges associated with these techniques, such as the impact of asthma medications on oocyte quality, the effects of hormonal stimulation on asthma control, and the risk of exacerbations during the IVF process. The review underscores the importance of collaborative efforts among healthcare providers, including allergists, pulmonologists, obstetricians, and fertility specialists, to ensure optimal management of asthmatic women seeking to conceive. It emphasizes the significance of preconception counseling, meticulous asthma control, appropriate medication management, and individualized fertility treatments to enhance the reproductive outcomes in this population.

Impact of immune checkpoint inhibition on ovarian reserve in patients with melanoma enrolled in the ECOG-ACRIN E1609 adjuvant trial.

12013 Background: Immunotherapy with immune checkpoint inhibition (ICI) is being widely adopted in the treatment of patients with a wide range of malignancies. However, we have no data on how these therapies influence fertility or ability to undergo fertility treatments after therapy. Within the melanoma community numerous women of childbearing age have been treated with ICI including ipilimumab, nivolumab and pembrolizumab. Anti-mullerian hormone (AMH) is a biomarker of ovarian reserve and a predictor of response to fertility treatments, including in vitro fertilization (IVF). In women under the age of 35 who have no reproductive pathology, AMH should be detectable and remain relatively stable over time. Above the age of 35 AMH decline accelerates as the number of eggs decreases more rapidly due to normal ovarian aging. Methods: Pre and post-treatment samples from women aged 20-35 whose melanoma was treated with 3 mg/kg ipilimumab (57%) or 10 mg/kg ipilimumab (43%) in the adjuvant setting on trial ECOG-ACRIN E1609 were analyzed in collaboration with the BWH Reproductive Endocrine Laboratory. Serum samples were tested for luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, AMH and prolactin. Results: Samples from E1609 were available from 28 female patients with a median age of 28 (min 20, max 35). The median time between samples was 8.0 months (min 0.7, max 16.4). 53% of patients had stage IIIB melanoma, 43% stage IIIC and one patient had M1a disease. AMH, estradiol and LH significantly decreased after treatment (p < 0.001, p = 0.016, p = 0.012, respectively) (Figure 1); there was no significant difference in the level of FSH and prolactin before and after the treatment (p = 0.68, p = 0.12, respectively). The median AMH was 4.24 ng/mL in the pre-treatment group and 3.51 in the post-treatment group. Conclusions: In this study of young women treated with ipilimumab there was a significant decrease in AMH before and after ICI therapy suggesting that ovarian reserve and possibly female fertility may be impacted by immune checkpoint inhibition. Further investigation is needed to look at PD-1 inhibition and combination immunotherapy effects on ovarian reserve and female fertility. In addition, there is a similar need to examine ICI effects on male fertility.

PD18-11 IMPACT OF STATE IN-VITRO FERTILIZATION MANDATES ON MALE INFERTILITY CARE

You have accessJournal of UrologyCME1 Apr 2023PD18-11 IMPACT OF STATE IN-VITRO FERTILIZATION MANDATES ON MALE INFERTILITY CARE James Dupree, Rodney L. Dunn, Phyllis Yan, David Suh, Erica Marsh, Edward C. Norton, Vanessa Dalton, and Marissa S. Weiss James DupreeJames Dupree More articles by this author , Rodney L. DunnRodney L. Dunn More articles by this author , Phyllis YanPhyllis Yan More articles by this author , David SuhDavid Suh More articles by this author , Erica MarshErica Marsh More articles by this author , Edward C. NortonEdward C. Norton More articles by this author , Vanessa DaltonVanessa Dalton More articles by this author , and Marissa S. WeissMarissa S. Weiss More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003273.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: By 2019, 11 states had passed laws mandating insurance coverage for infertility care, including in-vitro fertilization (IVF). These mandates vary in their coverage for male infertility care, with five states (AR, HI, IL, MD, RI) mandating IVF coverage but not coverage for male infertility care. Our objective was to evaluate the use of IVF and three common male infertility procedures (varicocelectomy, testicular/epididymal biopsy, and vasectomy reversal) in three groups of states: 1) states mandating IVF coverage and male infertility care, 2) states mandating IVF coverage but not male infertility care, and 3) states without IVF mandates. METHODS: We obtained nationwide insurance claims from over 80 million individuals from 2003 to 2019 from Optum® ClinformaticsTM Data Mart. We identified IVF cycles using the Current Procedural Terminology (CPT) code for oocyte retrieval and excluded oocyte retrievals performed for fertility preservation. We identified varicocelectomy, testicular/epididymal biopsy, and vasectomy reversal using their respective CPT codes. States were categorized into three groups: 1) states mandating IVF coverage and male infertility care (CT, MA, NJ, NY, DE 2018-19, UT 2018-19); 2) states mandating IVF coverage but not male infertility care (AR, HI, IL, MD, RI); and 3) all remaining states, including both DE and UT from 2003-2017. Within each group of states, we calculated the use rates and 95% confidence intervals (CIs) of IVF cycles per 100,000 women aged 21-44 and of varicocelectomy, testicular/epididymal biopsy, and vasectomy reversal per 100,000 men. RESULTS: IVF use was highest in Group 1 states and lowest in Group 3 states (Table 1). Varicocelectomy and testicular/epididymal biopsy use was 43% to 89% higher in Group 1 states than in Group 2 and 3 states. Use of vasectomy reversal—a procedure not typically covered by insurance regardless of state mandates—was only 14% higher in Group 1 states than in Group 3 states. The overall use of male infertility procedures was similar in Group 2 and 3 states. CONCLUSIONS: There is decreased use of male infertility procedures in states whose IVF mandates do not include coverage for male infertility care. Policymakers considering new state mandates for IVF should include coverage for male infertility care to facilitate access to effective male infertility treatments. Source of Funding: Eunice Kennedy Shriver National Institute of Child Health & Human Development - 1R01HD103603-01A1 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e507 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information James Dupree More articles by this author Rodney L. Dunn More articles by this author Phyllis Yan More articles by this author David Suh More articles by this author Erica Marsh More articles by this author Edward C. Norton More articles by this author Vanessa Dalton More articles by this author Marissa S. Weiss More articles by this author Expand All Advertisement PDF downloadLoading ...

Associations of Sperm mtDNA Copy Number, DNA Fragmentation Index, and Reactive Oxygen Species With Clinical Outcomes in ART Treatments

Recent studies have suggested that sperm mitochondrial DNA copy number (mtDNA-CN), DNA fragmentation index (DFI), and reactive oxygen species (ROS) content are crucial to sperm function. However, the associations between these measurements and embryo development and pregnancy outcomes in assisted reproductive technology (ART) remain unclear. Semen samples were collected from 401 participants, and seminal quality, parameters of sperm concentration, motility, and morphology were analyzed by a computer-assisted sperm analysis system. DFI, mtDNA-CN, and ROS levels were measured using sperm chromatin structure assay, real-time quantitative polymerase chain reaction, and ROS assay, respectively. Among the participants, 126 couples underwent ART treatments, including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), and 79 of the couples had embryos transferred. In 401 semen samples, elevated mtDNA-CN and DFI were associated with poor seminal quality. In 126 ART couples, only mtDNA-CN was negatively correlated with the fertilization rate, but this correlation was not significant after adjusting for male age, female age, seminal quality, ART strategy, number of retrieved oocytes, controlled stimulation protocols, and cycle rank. Regarding pregnancy outcomes, sperm mtDNA-CN, ROS, and DFI were not associated with the clinical pregnancy rate or live birth rate in 79 transferred cases. In conclusion, increased mtDNA-CN and DFI in sperm jointly contributed to poor seminal quality, but sperm mtDNA-CN, ROS, and DFI were not associated with clinical outcomes in ART.

Glucocorticoid therapy in assisted reproduction.

As glucocorticoids are well-known as important regulators of stress and the immune system, their function and clinical use have elicited substantial interest in the field of reproduction. In particular, the effect of glucocorticoid therapy on endometrial receptivity during assisted reproduction, including in vitro fertilization (IVF) cycles, has led to a great deal of interest and controversy. However, previous studies have not been able to provide consistent and reliable evidence due to their small, non-controlled designs and use of different criteria. Considering the potential risk of exposure to glucocorticoids for mothers and fetuses in early pregnancy, the use of glucocorticoids in IVF cycles should be carefully evaluated, including the balance between risk and benefit. To date, there is no conclusive evidence that the use of glucocorticoids improves the pregnancy rate in IVF cycles with unselected subjects, and a further investigation should be considered with a proper study design.

Conventional Laparoscopy Is the Better Option for Tubal Sterilization Reversal: A Closer Look at Tubal Reanastomosis.

Background: Permanent sterilization is one of the most common methods of birth control in the United States and around the world. A small subset of women will regret their decision and desire future fertility. For these women, the options include in vitro fertilization (IVF) or surgical reversal. Surgical reversal, specifically via tubal reanastamosis, is an important choice to consider. Surgical reversal can be accomplished via three different general approaches including laparotomy, conventional laparoscopy, and robot-assisted approaches. Unfortunately, surgical reversal is becoming a lost art.Objective: To compare and contrast pregnancy success rates, ectopic pregnancy rates, and cost between the surgical methods and IVF.Methods: We conducted a literature review via Pubmed with keywords as listed below.Conclusion: Laparoscopic tubal reanastomosis is the best approach for women <40 years of age due to pregnancy outcomes that are comparable to other methods, cost effectiveness, and favorable safety profile of minimally invasive surgery.

Long-Term Disturbed Expression and DNA Methylation of SCAP/SREBP Signaling in the Mouse Lung From Assisted Reproductive Technologies.

Assisted reproductive technology (ART) has been linked to cholesterol metabolic and respiratory disorders later in life, but the mechanisms by which biosynthetic signaling remain unclear. Lung inflammatory diseases are tightly linked with the sterol regulatory element-binding protein (SREBP) and SREBP cleavage-activating protein (SCAP), but this has not been shown in an ART offspring. Here, mouse models from a young to old age were established including in vitro fertilization (IVF), intracytoplasmic injection (ICSI), and in vivo fertilized groups. In our results, significantly higher plasma levels of CRP, IgM, and IgG were identified in the aged ICSI mice. Additionally, pulmonary inflammation was found in four aged ART mice. At three weeks, ART mice showed significantly downregulated levels of Scap, Srebp-1a, Srebp-1c, and Srebf2 mRNA in the lung. At the same time, significant differences in the DNA methylation rates of Scap-Srebfs and protein expression of nuclear forms of SREBPs (nSREBPs) were detected in the ART groups. Only abnormalities in the expression levels of Srebp-1a and Srebp-1c mRNA and nSREBP1 protein were found in the ART groups at 10 weeks. However, at 1.5 years old, aberrant expression levels and DNA methylation of SCAP, SREBP1, and SREBP2, and their associated target genes, were observed in the lung of the ART groups. Our results indicate that ART increases long-term alterations in SCAP/SREBP expression that may be associated with their aberrant methylation status in mouse.

COMPARATIVE STUDY BETWEEN DIFFERENT TYPES OF VAGINAL PROGESTERONE IN LUTEAL PHASE SUPPORT IN ICSI CYCLES

Background: Assisted reproductive techniques (ART) include all fertility treatments in which the gametes (egg and sperm) are handled outside the human body with the aim of achieving a healthy conception. Common ART procedures include in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI), fresh or frozen embryo transfer, and IVF with donor oocytes. Luteal phase support through pharmaceutical drugs has been universally agreed. Objective: To compare the effectiveness of different types of vaginal progesterone preparations for luteal support in patients undergoing Intracytoplasmic Sperm Injection. Patients and Methods: The current randomized controlled clinical trial study was conducted on 300 patients who were following at the Assisted Reproductive Technology (ART) unit of the International Islamic Center for Population Studies and Research (IICPSR) of Al-Azhar University over the period from May 2016 to January 2018 after being approved by the ethical committee. The patients were divided into 3 equal groups received Prontogest vaginal suppositories 400 mg once per day, Group B received Crinone 8% (90 mg) vaginal gel once per day and Group C received Endometrin vaginal suppositories once per day. Results: Comparison between studied group A (Prontogest), group B (Crinone) and group C (Endometrin) as regards demographic characteristics revealed no statistically significant differences. As regards the cause of infertility, a statistically significant increase in the number of patients with male and tubal factors in group B (Crinone) than group A (Prontogest). Concerning the laboratory hormonal profile of the studied groups before ICSI, there was a statistically significant increase in FSH and LH levels in group A (Prontogest) than group B (Crinone) and group C (Endometrin). On the other hand, there was a difference between the studied groups as regards prolactin and estrogen levels, but did not reach statistical significance. Comparison between studied groups, as regards Endometrial thickness, number of retrieved oocytes and number of transferred embryos revealed no statistically significant difference. Comparison between the studied groups, as regards pregnancy rates, revealed a statistically significant increase in pregnancy rates in group C than group A. Conclusion: The use of Endometrin vaginal suppositories in patients undergoing ICSI had a statistically significant higher clinical pregnancy rates in comparison to Prontogest vaginal suppositories. On the other hand, Crinone vaginal gel had a higher clinical pregnancy rate than Prontogest.

Placenta pathology in recipient versus donor oocyte derivation for in vitro fertilization in a setting of hypertensive disorders of pregnancy and IUGR

IntroductionAssisted reproductive technology including in vitro fertilization (IVF) and oocyte donation (OD) may increase risk for placenta-mediated diseases. Comprehensive analysis of histopathological placental lesions according to source of oocytes used in the IVF procedure – recipient derived (RD-IVF) vs oocyte donation (OD-IVF), has not been conducted in a population with a hypertensive disorder of pregnancy (HDP) and/or intrauterine growth restriction (IUGR). MethodsA retrospective cohort study of archived placenta specimens from RD-IVF and OD-IVF pregnancies affected by HDP and/or IUGR was conducted with blinded histopathological placental examination. Three categories of lesions were differentiated and defined as main outcomes: maternal vascular malperfusion (MVM), chronic inflammation, and fetal vascular malperfusion (FVM). To determine the relationship between conception method and placental lesions, multivariable regressions were performed with maternal age, gestational age, HDP, birth and placental weight percentiles as model covariates. Results115 placentas were included 83 (72.2%) RD-IVF, 32 (27.8%) OD-IVF. Adjusted OR (aOR) for conception method was 5.05 (95%CI 0.58–43.90, p=0.142) for MVM, 1.87 (95%CI 0.68–5.15, p=0.228) for chronic inflammatory and 0.61 (95%CI 0.15–2.37, p=0.471) for FVM lesions. Multiple gestation demonstrated borderline association with MVM (aOR=0.24, 95%CI 0.04–1.51, p=0.129) and total pathology score (aRR=0.79, 95%CI 0.62–1.01, p=0.058). Subgroup analysis suggested greater odds of villitis of unknown etiology (VUE) for OD-IVF (aOR=2.98, 95%CI 1.12–7.93, p=0.029). DiscussionSource of oocyte derivation demonstrated no evidence of association with main outcomes in cases of HDP and/or IUGR. Subgroup analysis demonstrated increased rates of inflammatory lesions for OD-IVF. Multiple gestation may be associated with decreased MVM and total lesions.

In-Vitro Fertilization Impact on the Risk of Breast Cancer: A Review Article.

Background:Due to the increasing prevalence of infertility, the number of referrals to infertility treatment centers has also increased. Nowadays, assisted reproductive technology (ART), including in vitro fertilization (IVF), is a treatment for infertility or genetic problems. Considering the possible consequences of this method among women undergoing in vitro fertilization (IVF) and kids conceived by IVF, extensive research has been conducted in this regard.Methods:Overall, 100 articles were entered into the study, and relevant articles were searched and extracted from PubMed, Springer, and Google Scholar databases. In IVF procedure, medications such as Clomiphene citrate and gonadotropins are used to stimulate and mature follicles and thus increase ovulation.Results:There are conflicting opinions on this issue. Some findings report a slight increase in cancer risk for hormone-sensitive cancers including breast cancer. The long-term use of IVF medications can increase estrogen hormones and cause excessive expression of genes, resulting in an increased risk of breast cancer, which is one of the most frequent cancers among women.Conclusion:There are some risks to be aware of, which followed the hypothesis that long IVF treatment process may lead to breast cancer among IVF candidates. Furthermore, the risk of breast cancer may be increased in those women with a positive family history and related inherited genes. Therefore, women candidates for IVF should be informed of the probable implications of the reproductive therapy techniques.

Isthmocele—a New Obstetric Surgery Sequela for Laparoscopic Surgeons

Cesarean section is a common obstetric surgery worldwide. It leads to hitherto unrecognized but not too uncommon sequela known as isthmocele—which is a cesarean section scar defect in the uterus which goes mostly unrecognized and is not cared for. It is certainly not asymptomatic nor totally benign. Such patients suffer from lower abdominal pain, abnormal menstrual bleeding, and secondary infertility including in vitro fertilization (IVF) failure, and they were not responding to a medical treatment. This defect was recognized in a case series of 17 patients and was successfully treated by a laparoscopy repair. Saline-filled hysteroscopy (5 mm) along with an ultrasound examination was the main diagnostic modality. The laparoscopic procedure under general anesthesia included adhesiolysis if any, the lower uterine segment scar excision assisted by transvaginal illumination, and intra-corporeal re-suturing of uterine defect using a number zero polyglycolic acid suture in 2 layers. The post-menstrual bleeding abated in all 17 patients; 6/17 desired a 2nd pregnancy and they are under observation.

SAT-433 The Influence of Thyroid Autoimmunity on Pregnancy Outcome in Infertile Women

Background: Women with subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) reportedly have high risks of miscarriage and preterm birth. Infertile women undergoing assisted reproductive technology (ART) are recommended for levothyroxine (L-T4) supplementation to maintain TSH levels below 2.5 mIU/mL according to ATA guideline; however, insufficient evidence exists to determine whether L-T4 treatment for infertile women with TSH levels between 2.5 and 5.0 mIU/mL. Objective: To clarify the influence of TAI on pregnancy in infertile women under L-T4 treatment to maintain TSH levels below 2.5 mIU/mL, and to compare its influence depending on fertility treatments. Methods: A total of 595 infertile women who visited a fertility clinic between January 2013 and December 2015 were prospectively recruited to this study. Five patients with Graves’ disease were excluded and remained 590 women were included in the analysis. Infertile women with TSH levels above 2.5 mIU/mL were treated with L-T4 followed by evaluation of fertility status and pregnancy outcomes. Factors affecting pregnancy were analyzed statistically depending on fertility treatments. Written informed consent was obtained from all patients, and the study protocol was approved by the Ethics Committee. Results: The proportion of SCH and thyroid peroxidase antibodies (TPOAb).positivity was 19.6% and 10.4%, respectively. Women who did not become pregnant were older than those who became pregnant (p=0.003), but no influence of thyroid-associated factors on pregnancy was confirmed. Pregnancy outcome contrarily showed that women who had a miscarriage were older (p<0.001) and higher TPOAb titers (p=0.038) than those who had a live birth. In addition, higher age (OR 26.4, p<0.001) and high TPOAb titer (OR 11.8, p=0.043) were decided as risk factors for miscarriage through multiple logistic regression analysis. Among women who treated with intrauterine insemination, TPOAb titers were higher in women who had a miscarriage than in those who had a live birth (p=0.040). We further focused on the difference between ART methods including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Women undergoing IVF had higher TPOAb titers in women who had miscarriage than those who had a live birth (p=0.023), but in women undergoing ICSI there was no association between TPOAb titers and pregnancy outcome. Conclusion: Infertile women with high TPOAb titers are susceptible to miscarriage despite appropriate L-T4 treatment. The influence of TPOAb titers as well as TPOAb positivity on pregnancy should be considered, when undergoing fertility treatments.

Mortality from infancy to adolescence in singleton children conceived from assisted reproductive techniques versus naturally conceived singletons in Sweden

To assess infant (<1 year) and childhood (1-18 years) mortality in singletons conceived through assisted reproductive techniques (ART) versus naturally conceived singletons. Nationwide prospective study. Sweden. All singleton liveborn infants born from 1983 to 2012 in Sweden identified using the Medical Birth Register (N = 2,847,108), of whom 43,506 were conceived through ART treatments including invitro fertilization with and without intracytoplasmic sperm injection. None. Infant (<1 year) and childhood (1-18 years) mortality. Data on ART treatment and covariates were retrieved from population-based registers using the unique personal identity number assigned to all permanent residents in Sweden. Cox proportional hazards models estimated the hazard ratios (HRs) with 95% confidence intervals (CIs) as measures of association between ART treatments and death. The analyses were adjusted for maternal characteristics, infertility, child sex, and birth cohort and were restricted to individuals with complete information on covariates for fully adjusted analysis. Compared with naturally conceived singletons, higher infant mortality risks were seen in infants conceived through ART (adjusted HR 1.45; 95% CI, 1.19-1.77), especially after transfer of cryopreserved embryos (adjusted HR 2.30; 95% CI, 1.46-3.64). Early neonatal mortality risk (deaths during the first week) was increased in children born after transfer of blastocysts (HR 2.40; 95% CI, 1.05-5.48). No increased mortality risk was observed between the ages of 1 and 18 years. Singletons conceived through ART had an increased risk of infant mortality from birth up to 1 year of life, predominantly in the early neonatal period and in pregnancies after transfer of frozen and thawed embryos.

Kualitas, Kemampuan Implantasi dan Viabilitas in-vivo Embrio Mencit (Mus muculus) Galur Swiss Webster Setelah Pembekuan Dengan Metode Vitrifikasi

Reproductive technologies including in vitro fertilization (IVF), embryo manipulation, gamete and embryo freezing, thawing and embryo transfer were rapidly developed. Vitrification is an embryo freezing technique that is the most developed. In this experiment, we vitrified mouse embryos and then examined the embryos i.e: (i) the quality of the embryos after thawing, (ii) the implantation rate of the embryos and (iii) viability of the embryos in vivo. Morulae and blastocycsts were collected from female mice that were pregnant a day 3,5. The embryos were equilibraten in mPBS +10% etilene glycol. Vitrification was carried out by using VABEDS medium, containing 6-10 embryos that were dropped into a tip of a straw, then frozen in liquid nitrogen for 24 hours. Thawing was carried out by flushing the embryos using mPBS suplemented with 0.5, 0.25, 0.1 and 0 M sucrose. After being incubated in M2 medium at 37oC for 1-2 hours, the recovery embryos were then transferred into the uteri of day 2.5 of pseudopregnat females. The females were then sacrificed at day 16 of gestation and the total implantaion, total life and death fetuses, as well as resorpted embryos, were taken as data. The results showed that vitrification significantly (p&lt;0,05) reduced the quality of the embryos, as well as their implantation rate and the viability of the fetuses, which may be caused by the unoptimal combination of the cryoprotectant in the vitrification medium, temperature and exposure time during vitrification.

IL-10 to TNFα ratios throughout early first trimester can discriminate healthy pregnancies from pregnancy losses.

Embryo implantation and placentation require a careful immunological balance. Cytokines such as IL-10 and TNFα have been implicated as markers of dysregulation, but have only been studied at a single time point or after a pregnancy loss. Our objective was to determine normative patterns of serum levels of IL-10 and TNFα and their ratio throughout the first trimester in healthy pregnancies and to determine if this pattern differs from pregnancy loss. Two prospective longitudinal cohorts of gravidae including in vitro fertilization (IVF) and naturally conceived pregnancies with serial blood draws. Cytokines were assayed using Simple Plex. In the IVF cohort, we monitored from the implantation day up to 6weeks of gestation; whereas in the naturally conceived cohort, sample collection began at 4weeks and throughout the whole first trimester. IL-10 concentrations in normal pregnancies were significantly higher than in pregnancies ending in a loss starting at 6-8weeks of gestation, while TNFα concentrations were significantly lower in normal than in pregnancies ending in a loss starting at 3-5 of gestation weeks. The IL-10 to TNFα ratio in normal pregnancies was significantly higher from 4 to 9weeks compared to pregnancies that were lost (t test, P<.05). Changes were observed before any symptoms of miscarriage were present. We provide evidences of differences in early immunomodulation in healthy pregnancies vs those destined to end in first-trimester loss. The ratio of IL-10 to TNFα rises significantly higher in viable pregnancies as early as 4.5weeks compared to pregnancies loss.

Is scanning for vasa previa important for singleton pregnancies that started as multiple conceptions?

ObjectivesVasa previa (VP) is a congenital placentation disorder in which fetal vessels run across the internal os of the cervix under the fetal presentation. This rare condition is associated with a high rate of perinatal morbidity and mortality when undetected before delivery. Roughly 85% of all cases of VP can be associated with one or more identifiable risk factors including in-vitro fertilization (IVF), multiple gestations, bilobed, succenturiate or low-lying placentas, and velamentous cord insertion (VCI). Recent evidence indicates the need for standardized prenatal targeted scanning protocols of pregnancies at risk of VP. The present study reports on pregnancies that began with multiple gestations but ended with a single fetus diagnosed with VP. Study designWe retrospectively collected and reviewed medical records from 2006 to 2018 of early multiple pregnancies that ended with a single fetus diagnosed with VP in our medical center, including three cases of twin gestation complicated by a vanishing twin and a case of multifetal reduction in triplet pregnancy. This retrospective cohort study was approved by our Institutional Clinical Research Committee. ResultsThe database search identified 50 pregnancies that started as multiple gestations but continued as singletons. Of these, 4 pregnancies were diagnosed with VP, for a prevalence of 8.0%. For two of the four cases, the diagnosis was made during delivery as expressed by a low Apgar score at 1 and 5 min, a low cord blood pH value, newborn resuscitation, blood product transfusion, and NICU supervision. There was a statistically significant difference in the prevalence of VP in pregnancies that started as multiple gestations but continued later as singletons compared to multiple pregnancies (8.0% vs. 0.2% respectively, p < 0.0001). The OR for VP in pregnancies that started as multiple gestations but continued as singletons was 41.1 (95% CI, 12.77–131.94). ConclusionsOur findings suggest there is an increased risk of VP in conceptions that started as viable multiple gestations but continued later as singletons. If our findings supported by others, it may be prudent to consider all twins at the beginning of pregnancy to be at risk for VP, irrespective of the actual number of life fetuses at later stages of gestation.