The association of female reproductive factors with history of cardiovascular disease: a large cross-sectional study.

BACKGROUND: This study aimed to explore the association of female reproductive factors (age at first birth (AFB), age at last birth (ALB), number of pregnancies, and live births) with history of cardiovascular disease (CVD). METHODS: A total of 15,715 women aged 20 years or over from the National Health and Nutrition Examination Surveys from 1999 to 2018 were included in our analysis. Weighted multivariable logistic regression analysis and restricted cubic spline (RCS) model were used to evaluate the association of AFB and ALB with history of CVD in women. Additionally, the relationship between the number of pregnancies, and live births and history of CVD was also explored. RESULTS: After adjusting for potential confounding factors, the RCS plot showed a U-curve relationship between AFB, ALB and history of CVD. Among them, AFB was associated with congestive heart failure (CHF), heart attack, and stroke in a U-shaped curve. Additionally, this U-shaped correlation also exists between ALB and CHF and stroke. However, the number of pregnancies and live births was liner positive associated with history of CVD, including coronary heart disease, CHF, angina pectoris, heart attack, and stroke. CONCLUSIONS: Women with younger or later AFB and ALB have higher odds of CVD in later life. Further study is warranted to verify the underlying mechanisms of this association.

BEYOND: a randomized controlled trial comparing efficacy and safety of individualized follitropin delta dosing in a GnRH agonist versus antagonist protocol during the first ovarian stimulation cycle.

STUDY QUESTION: How does a gonadotrophin-releasing hormone (GnRH) agonist versus a GnRH antagonist protocol affect ovarian response when using an individualized fixed daily dose of follitropin delta for ovarian stimulation? SUMMARY ANSWER: The BEYOND trial data demonstrate thatindividualized fixed-dose follitropin delta is effective when used in a GnRH agonist protocol, compared with a GnRH antagonist protocol, in women with anti-Müllerian hormone (AMH) ≤35 pmol/l and no increased risk of ovarian hyperstimulation syndrome (OHSS). WHAT IS KNOWN ALREADY: The efficacy and safety of an individualized fixed daily dose of follitropin delta (based on body weight and AMH) have been established in randomized controlled trials (RCTs) using a GnRH antagonist protocol. Preliminary study data indicate that individualized follitropin delta is also efficacious in a GnRH agonist protocol (RAINBOW trial, NCT03564509). There are no prospective comparative data using individualized follitropin delta for ovarian stimulation in a GnRH agonist versus a GnRH antagonist protocol. STUDY DESIGN, SIZE, DURATION: This is the first randomized, controlled, open-label, multi-centre trial exploring efficacy and safety of individualized follitropin delta dosing in a GnRH agonist versus a GnRH antagonist protocol in participants undergoing their first ovarian stimulation cycle for IVF/ICSI. A total of 437 participants were randomized centrally and stratified by centre and age. The primary endpoint was the number of oocytes retrieved. Secondary endpoints included ongoing pregnancy rates, adverse drug reactions (including OHSS), live births, and neonatal outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants (18-40 years; AMH ≤35 pmol/l) were enrolled at specialist reproductive health clinics in Austria, Denmark, Israel, Italy, the Netherlands, Norway, and Switzerland. The mean number of oocytes retrieved was compared between the GnRH agonist and antagonist protocols using a negative binomial regression model with age and AMH at screening as factors. Analyses were based on all randomized subjects, using a multiple imputation method for randomized subjects withdrawing before the start of stimulation. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 437 randomized subjects, 221 were randomized to the GnRH agonist, and 216 were randomized to the GnRH antagonist protocol. The participants had a mean age of 32.3 ± 4.3 years and a mean serum AMH of 16.6 ± 7.8 pmol/l. A total of 202 and 204 participants started ovarian stimulation with follitropin delta in the GnRH agonist and antagonist groups, respectively. The mean number of oocytes retrieved was statistically significantly higher in the agonist group (11.1 ± 5.9) versus the antagonist group (9.6 ± 5.5), with an estimated mean difference of 1.31 oocytes (95% CI: 0.22; 2.40, P = 0.0185). The difference in number of oocytes retrieved was influenced by the patients' age and ovarian reserve, with a greater difference observed in patients aged <35 years and in patients with high ovarian reserve (AMH >15 pmol/l). Both the GnRH agonist and antagonist groups had a similar proportion of cycle cancellations (2.0% [4/202] versus 3.4% [7/204]) and fresh blastocyst transfer cancellations (13.4% [27/202] versus 14.7% [30/204]). The estimated ongoing pregnancy rate per started cycle was numerically higher in the GnRH agonist group (36.9% versus 29.1%; difference: 7.74% [95% CI: -1.49; 16.97, P = 0.1002]). The most commonly reported adverse events (≥1% in either group; headache, OHSS, nausea, pelvic pain, or discomfort and abdominal pain) were similar in both groups. The incidence of early moderate/severe OHSS was low (1.5% for the agonist group versus 2.5% for antagonist groups). Estimated live birth rates per started cycle were 35.8% and 28.7% in the GnRH agonist and antagonist groups, respectively (treatment difference 7.15%; 95% CI: -2.02; 16.31; P = 0.1265). The two treatment groups were comparable with respect to neonatal health data for singletons and twins and for incidence of congenital malformations (2.7% and 3.3% for the GnRH agonist versus antagonist groups, respectively). LIMITATIONS, REASONS FOR CAUTION: All participants had AMH ≤35 pmol/l and were ≤40 years old. Clinicians should remain cautious when using a GnRH agonist protocol in patients with AMH >35 pmol/l (i.e. those with an increased OHSS risk). The incidence of OHSS in the GnRH antagonist group may have been lower if a GnRH agonist trigger had been allowed. Outcomes of transfers with cryopreserved blastocysts were not followed up, therefore the cumulative live birth rates and neonatal outcomes after cryotransfer are unknown. WIDER IMPLICATIONS OF THE FINDINGS: In women with AMH ≤35 pmol/l, an individualized fixed daily dose of follitropin delta resulted in a significantly higher number of oocytes retrieved when used in a GnRH agonist protocol compared with a GnRH antagonist protocol, with no additional safety signals observed and no additional risk of OHSS. Live birth rates following ovarian stimulation with individualized follitropin delta were not statistically different between the GnRH protocols; however, the trial was not powered to assess this endpoint. There were no safety concerns with respect to neonatal health after ovarian stimulation with follitropin delta in either protocol. STUDY FUNDING/COMPETING INTEREST(S): The trial was funded by Ferring Pharmaceuticals. EE, EP, and MS have no competing interests. AP has received research support from Ferring, and Gedeon Richter, and honoraria or consultation fees from Preglem, Novo Nordisk, Ferring, Gedeon Richter, Cryos, Merck A/S. BC has received consulting fees from Ferring and Merck, and his department received fees from Ferring to cover the costs of patient enrolment. MBS has received support to attend meetings and/or travel from Ferring, and was a board member for FertiPROTEKT e.V. until 2023. JS has received honoraria or consultation fees from Ferring and Merck, and support for attending meetings and/or travel from Ferring, Merck, and GoodLife. TS has received support/travel expenses from Ferring for attending a congress meeting, and participated in an advisory board for Merck. YS has received grants/research support from Ferring and support to attend a professional society congress meeting from Merck. RL and PP are employees of Ferring Pharmaceuticals. PP is a BOD member of PharmaBiome and owns stocks of Takeda Pharmaceuticals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT03809429; EudraCT Number 2017-002783-40. TRIAL REGISTRATION DATE: 7 April 2019. DATE OF FIRST PATIENT'S ENROLMENT: 2 May 2019.

Ovarian tissue transplantation: 10 years of experience at the Bologna University.

Objective: The efficiency of ovarian tissue transplantation (OTT) was established in terms of ovarian function recovery (95% of cases), number of live births (over 200 worldwide to date) and induction of puberty. Unfortunately, the lack of international registries and the fact that many centers have not yet reported their outcomes, lead to poor knowledge of the exact fertility data. The aim of the study is to describe our experience with OTT to restore ovarian function and fertility. Methods: This study was designed as a single-center, observational, retrospective, cohort study that includes women who underwent OTT between December 2012 and June 2023 at our center. After approval by the oncologist/hematologist, a small fragment of ovarian tissue was thawed and analyzed to detect the presence of micrometastases before OTT. Thawed ovarian tissue was grafted laparoscopically at multiple sites, including the remaining ovary and pelvic side wall (orthotopic transplantation) and/or abdominal wall (heterotopic transplantation). After OTT, ovarian function was monitored by hormonal assay, ultrasound and color Doppler at approximately 4-week intervals. Results: Between December 2012 and June 2023, 30 women performed OTT. Prior to OTT, immunohistochemical and molecular analyses revealed no micrometastases in all thawed ovarian tissue samples. In our series of 30 women, 20 of women were on premature ovarian insufficiency (POI), and the remaining ten cases still had oligomenorrhea and difficulty getting pregnant. Among the women with POI before OTT and at least 6 months follow-up, recovery of endocrine function was observed in all but one woman who underwent orthotopic transplantation (13 of 14 cases), in one out of two women who underwent both orthotopic and heterotopic transplantation (1 of 2 cases) and in all women who underwent heterotopic transplantation (4 of 4 cases). Women who underwent OTT to enhance fertility had no alterations in menstrual cycle and hormonal levels. In total, ten pregnancies were obtained in 25 women, resulting in four live births, two ongoing pregnancies and four spontaneous abortions. Conclusion: Our data can help patients and physicians in their discussions and decisions about the need and possibilities of preserving fertility.

Living-Donor Uterus Transplantation: A Clinical Review.

Uterus transplantation (UTx) is currently the only available treatment for absolute uterine factor infertility. More than 90 uterus transplantations have been performed worldwide, mostly from living donors. Living-donor (LD) UTx is a challenging surgical procedure since it poses ethical issues, and it is a high-risk and invasive surgery with higher hysterectomy-related risks compared to conventional hysterectomy. A total of 59 living-donor hysterectomies have been reported in the literature, including 35 performed with a laparotomic approach, 20 with a robotic approach and 4 with a laparoscopic approach. The mean donor age was 45.6 ± 9.1 years, and 22 were unrelated with the recipients, 34 were emotionally related (27 mothers, 5 sisters, 2 mother's sisters). The mean recipient age was 28.8 ± 4.5 years. Mayer-Rokitansky-Küster-Hauser syndrome was the most common indication for uterus transplant. Robotic living-donor hysterectomy had the longest operative time but resulted in a lower blood loss and postoperative stay compared to laparotomic and laparoscopic approaches. Twenty-nine births from LD-UTx have been reported, four after robotic living-donor hysterectomy and twenty-five after a laparotomic procedure. UTx is now an effective treatment for women with UFI. While living-donor UTx in some cases may be considered an experimental procedure, it offers the extraordinary possibility to give women the opportunity to have a pregnancy. Many efforts should be made to reduce the potential risks for donors, including the use of mini-invasive techniques, and the efficacy of UTx in the recipients, giving the potential harm of immunosuppression in a recipient of a non-life-saving organ.

Association between gestational exposure to solar activity and pregnancy loss using live births from a Massachusetts-based medical center.

BACKGROUND: Solar activity has been linked to biological mechanisms important to pregnancy, including folate and melatonin levels and inflammatory markers. Thus, we aimed to investigate the association between gestational solar activity and pregnancy loss. METHODS: Our study included 71,963 singleton births conceived in 2002-2016 and delivered at an academic medical center in Eastern Massachusetts. We studied several solar activity metrics, including sunspot number, Kp index, and ultraviolet radiation, with data from the NASA Goddard Space Flight Center and European Centre for Medium-Range Weather Forecasts. We used a novel time series analytic approach to investigate associations between each metric from conception through 24 weeks of gestation and the number of live birth-identified conceptions (LBICs) -the total number of conceptions in each week that result in a live birth. This approach fits distributed lag models to data on LBICs, adjusted for time trends, and allows us to infer associations between pregnancy exposure and pregnancy loss. RESULTS: Overall, the association between solar activity during pregnancy and pregnancy loss varied by exposure metric. For sunspot number, we found that an interquartile range increase in sunspot number (78·7 sunspots) in all of the first 24 weeks of pregnancy was associated with 14·0 (95% CI: 6·5, 21·3) more pregnancy losses out of the average 92 LBICs in a week, and exposure in weeks ten through thirteen was identified as a critical window. Although not statistically significant, higher exposure to Kp index and to UV radiation across all 24 weeks of pregnancy was associated with more and less pregnancy losses, respectively. CONCLUSION: While exposure to certain metrics of solar activity (i.e., sunspot number) throughout the first 24 weeks of pregnancy may be associated with pregnancy losses, exposure to other metrics were not. Solar activity is a complex phenomenon, and more studies are needed to clarify underlying pathways.

Assessing the Impact of High Body Mass Index (BMI) on the Efficacy of Assisted Reproductive Technologies (ART) in Saudi Women: A Cross-Sectional Study Examining Ovarian Reserve and Treatment Outcomes.

INTRODUCTION: The global surge in high body mass index (BMI) and obesity has led to various health complications. While numerous studies have shown that obesity disrupts female fertility, the specific effects of obesity on the success rate of assisted reproductive technology (ART) treatments in Saudi women have been less explored. This study aimed to delve into this gap, especially focusing on the correlation between BMI, ovarian reserve parameters, and ART outcomes among Saudi women. METHODS: A cross-sectional study was carried out from January to August 2023, concentrating on Saudi women aged 18 and above who underwent ART treatments for infertility. A total of 1071 women participated, with 155 completing an online survey and 916 responding through a hard copy from several Saudi hospitals. The data encompassed demographics, medical history, anthropometric details, ovarian reserve parameters, and ART results. For the analysis, Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 28.0, Armonk, NY) was utilized, applying descriptive statistics, the Chi-square test, and a linear regression model to discern connections between BMI, participant characteristics, and ART outcomes. A p-value of less than 0.05 was considered statistically significant. RESULTS: Most participants were aged 25-34 (406) years and held a bachelor's degree (707). Over half (560) received fertility treatments in the past, with 37.9% (406) having polycystic ovary syndrome (PCOS) and 23.5% (252) with other fertility-impacting medical conditions. Interestingly, 62.1% (665) had not undergone any ART cycles. Of those who did, 51.6% (553) had clinical pregnancies leading to live births. About 23.8% (308) of those with clinical pregnancies faced miscarriages without successful live births. Furthermore, 17.6% (189) reported complications or side effects from past ART procedures, and 31.4% (336) were on ART-related medications or supplements. The linear regression highlighted that individuals with normal weight tended to undergo more ART cycles. However, those with a higher BMI exhibited increased chances of achieving clinical pregnancies and live births. CONCLUSION: The study underscores the crucial relationship between BMI and ART efficacy in Saudi women. The data reveals that BMI can significantly influence ART treatment outcomes, especially concerning the number of cycles, clinical pregnancies, and live births. Consequently, BMI should be an essential consideration when evaluating and optimizing the success rates of ART procedures.

Live birth per embryo transfer with next generation sequencing preimplantation genetic testing: an analysis of 26,107 cycles.

The technique and platform used for preimplantation genetic testing for aneuploidy (PGT-A) have undergone significant changes over time. The contemporary technique utilizes trophectoderm biopsy followed by next-generation sequencing (NGS). The goal of this study was to explore the role of PGT-A using NGS technique exclusively in contemporary in vitro fertilization (IVF) practice. For this, we performed a retrospective analysis of a large dataset collected from the Shady Grove Fertility (SGF) multicentre practice. All autologous IVF cycles which were followed by at least one single embryo transfer (ET) (fresh and/or frozen) between January 2017 to July 2020, were included. Our study group included patients who had PGT-A and the control group included patients who did not proceed with PGT-A. The primary outcome was the live birth rate (LBR) per transfer. All age-adjusted LBR was higher in the PGT-A group than the non-PGT-A group (48.9% vs. 42.7%, p < 0.001), except in women <35 years old among single embryo frozen ETs. Similarly, LBR in the PGT-A group was higher in all ages except in women <35 years old (48.7% vs. 41.7%, p < 0.001) when all single embryos fresh and frozen ETs were included. In patients of decreased ovarian reserve, transfer of euploid embryo was associated with higher LBR (46.7% vs. 26.7%, p < 0.001) whereas miscarriages were lower in patients with unexplained infertility (9.3% vs. 11.3%, p = 0.007 and endometriosis (8.9% vs. 11.6%, p < 0.001) following euploid embryo transfer. To conclude, the transfer of euploid embryos tested via NGS PGT-A was associated with improved LBR per transfer in women ≥35 years old.

The Fischer protocol for assisted reproductive technology treatment: Real-world data experience comparing elective single versus double embryo transfer with or without comprehensive chromosome screening.

High rates of multiple implantation after assisted reproductive technology (ART) treatment represent one of the major problems for both mothers and their fetuses. Given the availability of techniques intended to identify embryos with the highest chance for development to term, such as comprehensive chromosome screening (CCS) and blastocyst transfer, the decision on the number of embryos to transfer deserves careful consideration. This report presents real-life data from two clinics using the Fischer protocol for cycle programming in patients undergoing ART. Our data indicate that ovarian stimulation using the Fischer protocol provides consistent and optimal ART outcomes in centers following strict quality management standards. However, high multiple implantation rates were observed in fresh and frozen transfer cycles after transferring two embryos - even in patients aged over 39 years. The live birth rates after CCS were superior to those using untested embryos. These findings were held for the three age groups irrespective of the CCS culture day (D1 = PN stages, or D5 = blastocysts). Our results support a single embryo transfer policy, particularly in women under 34 years of age with favorable conditions during ART treatment, i.e., a high number of available fertilized oocytes.

Congenital Heart Disease and Fertility: A Danish Nationwide Cohort Study Including Both Men and Women.

Background Despite an increasing number of patients with congenital heart disease (CHD) reaching reproductive age, the fertility of these patients remains undescribed. Therefore, the aim of the study was to evaluate the fertility in men and women with CHD by estimating the risk of infertility and comparing the birth rates, proportions of individuals becoming parents or remaining childless, and the number of children per parent with unaffected individuals. Methods and Results The study population consisted of individuals born between 1977 and 2000. Information on CHD, infertility, and live born children were obtained from the Danish health registries. Hazard ratios for infertility were analyzed using a Cox regression model. Differences of proportions and birth rates were calculated and compared between groups. Among 1 385 895 individuals, a total of 8679 (0.6%) were diagnosed with CHD. Men and women with simple or moderate CHD had no increased risk of infertility when compared with the reference population. Estimates for complex CHD groups were too imprecise for evaluation. Individuals with CHD were more often childless with consequently lower birth rates compared with unaffected individuals. However, those becoming parents had the same number of children as the reference population. Conclusions Men and women with simple or moderate CHD had the same risk of infertility as the reference population. Despite patients with CHD more often being childless, those becoming parents had the same number of children as parents without CHD. The current findings increase the knowledge regarding fertility in the CHD population.

Influence of social, demographic, and clinical factors in live births with spinal dysraphism in Brazil: an ecological study of 21 years.

OBJECTIVES: This study aimed to verify possible associations between sociodemographic and clinical factors in live births with spinal dysraphism. METHODS: An analytical (descriptive and inferential) and ecological study was carried out based on secondary data of 11,308 live births with spinal dysraphism registered in the Live Birth Information System (SINASC) in Brazil from 1999 to 2019. Demographic factors analyzed were age, education, mothers' marital status and geographic region. The clinical factors analyzed were duration, gestation period, birthweight, and number of prenatal visits performed by women who underwent medical follow-up. RESULTS: There was an increase in the number of cases of spinal dysraphism in recent years in Brazil with an annual percentage variation of 3.52%. However, the period from 2005 to 2009 showed a reduction in live births with spinal dysraphism. The regions with the highest incidence were the South and Southeast. The risk increased in mothers born after 1980, older than 30 years and with a high level of education. The risk was increased in live births of whites and blacks, born from double pregnancy and with body weight less than 3000 g. The absence of prenatal care was associated with a higher incidence. CONCLUSION: Sociodemographic and clinical factors have specific characteristics that can predict spinal dysraphism in newborns in Brazil.

Expectant management of advanced abdominal pregnancies: Is it justifiable?

OBJECTIVE: To evaluate the outcome of a case series of women with advanced abdominal pregnancies (AAP) who underwent expectant management. STUDY DESIGN: A retrospective study that utilized prospective data of 46 women who were admitted for expectant management at a tertiary hospital in Durban, South Africa. All data was analyzed descriptively and presented in percentages. RESULTS: The average period of expectant management was 27 days; thirty-three (72 %) of the 46 women were discharged from the hospital with live babies. There were 11 (24 %) neonatal deaths and two cases of stillbirths. There were no maternal deaths and morbidity was minimal. CONCLUSION: When diagnosed after the 24th week of gestation, an option is expectant management which includes careful patient selection, prolonged hospitalization, and close antenatal fetal and maternal surveillance to achieve fetal viability. Management by experienced clinicians and a multidisciplinary team in a tertiary institution is recommended. Informed consent needs to take into consideration the risks with interventional laparotomy, social separation from family and friends, and the guarded perinatal outcome.

Chromosomal polymorphisms in assisted reproduction: a systematic review and meta-analysis.

This systematic review and meta-analysis investigated the effects of chromosomal polymorphisms in reproductive outcomes following IVF or ICSI. Literature in CENTRAL, CINAHL, EMBASE and MEDLINE were searched from 1974 to March 2020 with no language restrictions. Ten published cohort studies were chosen for analysis. Studies included females, males and couples undergoing assisted reproductive treatments with the presence or absence of chromosomal polymorphisms. Reproductive outcomes were reported and their quality assessed using the Newcastle-Ottawa Quality Assessment Scale. Meta-analysis of five cohort studies (9,659 participants) indicated that female carriers with chromosomal polymorphisms had a higher miscarriage rate compared to non-carriers (risk ratio (RR) 1.54 (95% CI 1.19-1.98), whereas no significant association was found for males (RR 0.96, 95% CI 0.64-1.43) and couples (RR 1.93, 95% CI 0.32-11.83) indicating that this effect appeared to be gender-dependent. There was no association between chromosomal polymorphisms and a higher rate of biochemical, clinical, ongoing pregnancy, and preterm and live birth.

Avaliação da completude dos dados do sistema de informação sobre nascidos vivos de imigrantes e brasileiros no estado do Paraná, 2014-2019 / Evaluation of the completeness of data in the information system on live births of immigrants and brazilians in the state of Paraná, 2014-2019 / Evaluación de la completitud de los datos del sistema de información sobre nacidos vivos de inmigrantes y brasileños en el estado de Paraná, 2014-2019

Avaliar a completude dos dados no SINASC do Paraná, entre 2014 a 2019, de imigrantes e brasileiros. Método: Estudo transversal, retrospectivo, de análise de completude dos dados de nascimento do ano de 2014 a 2019 no estado do Paraná. Foram critérios de análise: excelente (menos de 5% de incompletude); bom (5% a 10%); regular (10% a 20%); ruim (20% a 50%); e muito ruim (acima de 50%). Resultados: Foram registrados no Brasil 948.316 nascidos vivos, dos quais 935.629 eram de mães brasileiras e 12.867 de mães imigrantes de diversas nacionalidades. Dentre as variáveis, os campos incompletos de mães brasileiras somaram 50.243 (5,37%) e de imigrantes 696 (5,41%), demonstrando um bom preenchimento do banco. Conclusão: Foi possível verificar que o banco de dados SINASC mostrou-se confiável e com baixas incompletudes entre os anos de 2014 a 2019 no estado do Paraná, independente da naturalidade da mãe. Porém, dados incompletos referentes às imigrantes ainda são maiores comparados aos de mulheres brasileiras, podendo ser resultado de uma falta de capacitação dos profissionais da saúde para a comunicação com as mães imigrantes que não falam a língua nativa, não coletando os dados de forma adequada e completa.

To evaluate the completeness of data in the SINASC of Paraná, from 2014 to 2019, of immigrants and Brazilians. Method: Cross-sectional, retrospective study, of analysis of completeness of birth data from the year 2014 to 2019 in the state of Paraná. Analysis criteria were: excellent (less than 5% incompleteness); good (5% to 10%); fair (10% to 20%); bad (20% to 50%); and very bad (above 50%). Results: In Brazil, 948,316 live births were registered, of which 935,629 were from Brazilian mothers and 12,867 from immigrant mothers of various nationalities. Among the variables, the incomplete fields of Brazilian mothers totaled 50,243 (5.37%) and of immigrants 696 (5.41%), de- monstrating a good completion of the bank. Conclusion: It was possible to verify that the SINASC database proved to be reliable and with low incompleteness between the years 2014 to 2019 in the state of Paraná, regardless of the mother's naturality. However, in- complete data referring to immigrants are still higher compared to those of Brazilian wo- men, which may be the result of a lack of training of health professionals for communi- cation with immigrant mothers who do not speak the native language, not collecting the data properly and completely.

Evaluar la completitud de datos en el SINASC de Paraná, de 2014 a 2019, de inmigrantes y brasileños. Método: Estudio transversal, retrospectivo, de análisis de completitud de datos de nacimiento del año 2014 a 2019 en el estado de Paraná. Los criterios de análisis fueron: excelente (menos de 5% de incompletitud); bueno (5% a 10%); regular (10% a 20%); malo (20% a 50%); y muy malo (más de 50%). Resultados: En Brasil se registraron 948.316 nacidos vivos, de los cuales 935.629 eran de madres brasileñas y 12.867 de madres inmigrantes de diversas nacionalidades. Dentre as variá- veis, os campos incompletos de mães brasileiras somaram 50.243 (5,37%) e de imigrantes 696 (5,41%), demonstrando um bom preenchimento do banco. Conclusão: Foi possível verificar que o banco de dados SINASC mostrou-se confiável e com baixa incompletudes entre os anos de 2014 a 2019 no estado do Paraná, independentemente da naturalidade da mãe. Sin embargo, los datos incompletos referidos a las inmigrantes siguen siendo más altos en comparación con los de las mujeres brasileñas, lo que puede ser el resultado de la falta de formación de los profesionales de la salud para la comunicación con las madres inmigrantes que no hablan el idioma nativo, no recogiendo los datos de forma adecuada y completa.

Mendelian randomization analysis of factors related to ovulation and reproductive function and endometrial cancer risk.

BACKGROUND: Observational epidemiological studies suggest a link between several factors related to ovulation and reproductive function and endometrial cancer (EC) risk; however, it is not clear whether these relationships are causal, and whether the risk factors act independently of each other. The aim of this study was to investigate putative causal relationships between the number of live births, age at last live birth, and years ovulating and EC risk.  METHODS: We conducted a series of observational analyses to investigate various risk factors and EC risk in the UK Biobank (UKBB). Additionally, multivariate analysis was performed to elucidate the relationship between the number of live births, age at last live birth, and years ovulating and other related factors such as age at natural menopause, age at menarche, and body mass index (BMI). Secondly, we used Mendelian randomization (MR) to assess if these observed relationships were causal. Genome-wide significant single nucleotide polymorphisms (SNPs) were extracted from previous studies of woman's number of live births, age at menopause and menarche, and BMI. We conducted a genome-wide association analysis using the UKBB to identify SNPs associated with years ovulating, years using the contraceptive pill, and age at last live birth. RESULTS: We found evidence for a causal effect of the number of live births (inverse variance weighted (IVW) odds ratio (OR): 0.537, p = 0.006), the number of years ovulating (IVW OR: 1.051, p = 0.014), in addition to the known risk factors BMI, age at menarche, and age at menopause on EC risk in the univariate MR analyses. Due to the close relationships between these factors, we followed up with multivariable MR (MVMR) analysis. Results from the MVMR analysis showed that number of live births had a causal effect on EC risk (OR: 0.783, p = 0.036) independent of BMI, age at menarche and age at menopause. CONCLUSIONS: MVMR analysis showed that the number of live births causally reduced the risk of EC.

Temporal trend and spatial distribution of gestational and congenital syphilis in the State of Espírito Santo from 2010 to 2019. / Tendencia temporal y distribución espacial de la sífilis gestacional y congénita en el Estado de Espírito Santo de 2010 a 2019. / Tendência temporal e distribuição espacial das sífilis gestacional e congênita no Estado do Espírito Santo entre 2010 a 2019

Objective: To evaluate the temporal trend and spatial distribution of gestational and congenital syphilis in the State of Espírito Santo from 2010 to 2019. Materials and methods: This is an ecological time series study with data on gestational and congenital syphilis obtained from the National System of Diseases and Notifications (SINAN) and live births in the Information System on Live Births (SINASC). Incidence rates of gestational and congenital syphilis were calculated, which were grouped according to the IBGE health macro-regions and analyzed in biennia. Results: 9,763 cases of gestational syphilis and 3,912 cases of congenital syphilis were reported. Gestational syphilis rates ranged from 1.46 in 2013 to 31.49 cases per 1,000 live births in 2018, congenital syphilis rates ranged from 0.12 in 2010 to 11.51 cases per 1,000 live births in 2017. The South region had the lowest incidence rates (2.32 cases/1,000 live births for gestational syphilis and 0.54/1,000 live births for congenital syphilis) and the Metropolitan region the highest (37.08 cases/1,000 live births for gestational syphilis and 13.74/1,000 live births for congenital syphilis). Conclusion: The increase in cases of the disease suggests a deficiency in the quality of prenatal care.

Objetivo: Avaliar a tendência temporal e a distribuição espacial da sífilis gestacional e congênita no Estado do Espírito Santo de 2010 a 2019. Materiais e métodos: Trata-se de um estudo ecológico de série temporal com dados sobre sífilis gestacional e congênita obtidos do Sistema Nacional de Agravos e Notificações (SINAN) e de nascidos vivos no Sistema de Informação sobre os Nascidos Vivos (SINASC). Foram calculadas taxas de incidência de sífilis gestacional e congênita, que foram agrupadas conforme as macrorregiões de saúde do IBGE e analisadas em biênios. Resultados: Foram notificados 9.763 casos de sífilis gestacional e 3.912 casos de sífilis congênita. As taxas de sífilis gestacional variaram de 1,46 em 2013 a 31,49 casos por 1.000 nascidos vivos em 2018, as taxas de sífilis congênita, por sua vez, variaram de 0,12 em 2010 a 11,51 casos por 1.000 nascidos vivos em 2017. Quanto às macrorregiões, a região Sul apresentou as menores taxas de incidência (2,32 casos/1.000 nascidos vivos para sífilis gestacional e 0,54/1.000 nascidos vivos para sífilis congênita) e a região Metropolitana as maiores (37,08 casos/1.000 nascidos vivos para sífilis gestacional e 13,74/1.000 nascidos vivos para sífilis congênita). Conclusão: O aumento dos casos da doença sugere deficiência na qualidade do pré-natal.

Adverse drug reactions following lymphocyte immunotherapy for the treatment of infertility: A retrospective study.

AIM: Unexplained infertility is a major burden for couples who want to have children. Lymphocyte immunotherapy (LIT) could be a therapeutic help for these couples. Although LIT has been carried out for decades, the data on the success of therapy are still controversial and there is hardly information on possible adverse drug reactions. METHODS: In this study, we used a questionnaire to determine the frequency of local and systemic adverse drug reactions in our patients who were treated with LIT between 2017 and 2020 (n = 302). In addition, we asked about pregnancies and/or live births after LIT in a 2-year follow-up (n = 140). RESULTS: Most of the patients reported the occurrence of mild local adverse drug reactions in a period of less than 4 weeks: Over 75% reported moderate erythema, itching or swelling, over 10% erythema, itching or swelling as more pronounced adverse drug reaction. Blistering was specified in 10% of the cases. Serious adverse drug reactions or adverse events were not described. In the follow-up, 69% of our patients stated a pregnancy after LIT, and 50% a life birth. CONCLUSIONS: Overall, LIT represents a well-tolerated therapy for couples with unexplained infertility, however, more evidence is needed on the benefits.

Competition, insurance mandates, and clinical practices and outcomes at in vitro fertilization clinics.

PURPOSE: The high cost of in vitro fertilization (IVF) procedures coupled with public availability of success rates may influence IVF practice patterns and success rates but may be mitigated by mandated insurance coverage for IVF procedures. This study examined associations of competition with IVF practice patterns and success rates by insurance mandate status. METHODS: We used publicly available 2018 National Assisted Reproductive Technology Surveillance System data from the CDC. We defined competition as distance to nearest clinic and number of clinics within certain radii. We used linear regression to explore associations of competition, insurance mandate status, and interactions between competition and mandate status with clinical practice patterns (e.g., percentage of cycles among patients < 35 years, percentage of cycles using ICSI, average number of embryos transferred) and IVF success rates (e.g., live birth rates). We also assessed the percentage of variation in outcomes explained by our models, R2. RESULTS: For practice patterns, the largest R2 value was 0.3518, meaning only 35.18% of the variability in the practice pattern variable was explained by competition and insurance mandate status. In most cases, the R2 values were less than 0.20, indicating little to no association. Less than 10% of the variability in success rates was explained by competition and insurance mandate status. CONCLUSION: The multiple regression analyses all yielded low R2 values, indicating weak associations. These encouraging results coincide with previous studies, suggesting that competition, even by insurance mandate status, does not have a strong association with IVF practice patterns or success rates.

Reconstructable Uterus-Derived Materials for Uterus Recovery toward Efficient Live Births.

Uterine factor infertility is increasingly common in modern society and has severely affected human life and health. However, the existing biomaterial scaffold-mediated systems remain limited in efficient uterus recovery, leading to low pregnancy rate and live births. Here, reconstructable uterus-derived materials (RUMs) are demonstrated by combining uterus-derived extracellular matrix and seeded chorionic villi mesenchymal stem cells for uterus recovery, achieving highly efficient live births in rats with severe uterine injury. The RUMs can be designed into different states (such as, liquid RUMs and solid RUMs) and shapes (such as, cuboid, triangular-prism, and cube) in terms of requirements. The RUMs can effectively prevent intrauterine adhesion, and promote endometrial regeneration and muscle collagen reconstruction, as well as, accelerate wound healing by constructing a physical barrier and secreting cytokines, allowing efficient uterus recovery. The injured uterus nearly achieves complete recovery after treating with the RUMs and has normal pregnancies for supporting fetal development and live births, similar to the normal rats. The study provides a regenerative medicine therapeutics for uterine factor infertility.

Cancer treatment is associated with a measurable decrease in live births in a large, population-based study.

OBJECTIVE: To define the live birth rates in a large, population-based study of the most common reproductive-age cancers in women. DESIGN: Retrospective cohort study. SETTING: Population-based study. PATIENTS: Female cancer patients diagnosed with cancer at age 18 years old or older between 1952-2014 (n = 17,952) were compared to fertility of non-cancer controls (n = 89,436). INTERVENTIONS: Live births in cancer survivors were compared with those in healthy, age-matched controls. Cases and controls were matched in the ratio of 5:1 for birth year, birthplace (Utah, yes/no), and follow-up time in Utah. MAIN OUTCOME MEASURE: Rate of at least one live birth, reported as an incidence rate ratio (IRR). RESULTS: Of all cancer survivors, 3,127 (17.4%) had at least 1 live birth after treatment in comparison to 19,405 healthy, age-matched controls (21.7%) with the same amount of time exposure for attempting pregnancy. Breast cancer was the most common cancer type (23.1% of patients in cohort). Compared with age-matched, healthy controls, IRR of live birth was 0.69 (95% confidence interval [CI], 0.67-0.70) for all cancer types, 0.25 (95% CI, 0.20-0.33) for leukemia, 0.40 (95% CI, 0.28-0.59) for gastrointestinal cancers, 0.44 (95% CI, 0.41-0.48) for breast cancer, 0.53 (95% CI, 0.47-0.59) for central nervous system cancers, and 0.57 (95% CI, 0.44-0.73) for soft tissue cancers. With all cancer types stratified by age at diagnosis, IRR for live births in cancer survivors aged >41 years at diagnosis was 0.48 (95% CI, 0.44-0.52); IRR was 0.64 (95% CI, 0.61-0.67) in the group aged 31-40 years and 0.71 (95% CI, 0.69-0.74) in the group aged 18-30 years after their cancer treatment. CONCLUSIONS: Cancer and its treatment were associated with lower live birth rates when comparing women with cancer vs. age-matched, healthy controls.