Probability Of Birth Research Articles

Is There a Relationship between Sperm DNA Fragmentation and Intra-Uterine Insemination Outcome in Couples with Unexplained or Mild Male Infertility? Results from the ID-Trial.

Sperm DNA fragmentation has been proposed as a candidate test for the assessment of sperm function on the premise that damage to the sperm chromatin is associated with a detrimental reproductive outcome. The objective of our study was to investigate whether sperm DNA fragmentation testing has a prognostic value, and thus can play a pivotal role in selecting future patients for intra-uterine insemination (IUI) therapy. This was a prospective cohort study conducted in a University Hospital setting. SDF was measured through TUNEL assay on the fresh semen sample presented at diagnosis and at insemination in couples with idiopathic/mild male infertility undergoing natural cycle IUI treatment. The generalized estimating equation (GEE)-model and multivariable model were used to analyze the probability of live birth and clinical pregnancy, respectively. ROC analysis was carried out to determine an SDF cut-off. There was an inverse relationship between SDF in the ejaculate of the diagnostic semen sample and CP (p = 0.02; OR 0.94 95% CI (0.90, 0.989)) as well as LB (p = 0.04; OR 0.95 95% CI (0.90, 0.9985)). No significant association was found between SDF after gradient and IUI outcome in the diagnostic sample nor between SDF (ejaculate/after gradient) in the IUI samples. The ROC analysis proposed a cutoff of 17.5% as the best compromise between sensitivity and specificity in the diagnostic SDF for live birth; however, the test diagnostics are low, with an AUC of 0.576. Overall, this study strengthens the hypothesis of an inverse relationship between SDF and CP/LB. Furthermore, SDF taken together with other clinical characteristics might provide more insight into male reproductive potential and predicting IUI outcome. Couples with SDF ≥ 17.5% in the diagnostic semen sample did not reach live birth. Further research is necessary to establish the diagnostic and prognostic potential of SDF as an add-on test.

Air pollution exposure and pregnancy outcomes among women with polycystic ovary syndrome.

Recently, the relationship between air pollution and reproductive outcomes has become a research focus. However, there is a lack of research on the relationship between air pollution and polycystic ovary syndrome (PCOS). This is a retrospective cohort study included a total of 1,652 women with PCOS and 12,543 women without PCOS conducted from 1 January 2015 to 31 December 2019. The average daily concentration data of six air pollutants (PM2.5, PM10, O3, NO2, SO2, and CO) during different exposure windows were obtained. Generalized estimating equation models were used to evaluate the association of air pollution with pregnancy outcomes. Air pollutants were not found to have a significant association with pregnancy rates among patients with PCOS. However, each IQR increase in PM10 exposure during period 3 (embryo transfer to serum HCG test) was associated with the reduced clinical pregnancy rate (adjusted OR = 0.92, 95% CI: 0.84-0.99) for patients without PCOS. Patients without PCOS showed lower clinical pregnancy rates with increased exposure to NO2 during periods 2 (oocyte retrieval to embryo transfer) and 5 (start of gonadotropin medication to embryo transfer), with aORs and 95% CIs of 0.94 (0.88, 0.99) and 0.94 (0.88, 0.98), respectively. Each IQR increase in SO2 among patients without PCOS during periods 1 (start of gonadotropin medication to oocyte retrieval), 2, 5, and 6 (start of gonadotropin medication to serum HCG test) was related to a decrease in clinical pregnancy rate. For the live birth rate, no significant relationship was found between air pollutants, including PM2.5, PM10, SO2, NO2, CO, and O3, and the live birth rate for women with PCOS. However, women without PCOS presented a lower probability of live birth with exposure to SO2 during periods 1, 2, 5, and 6. This retrospective study of reproductive-aged women observed no significant relationships between ambient pollutants and pregnancy outcomes among women with PCOS but found negative associations among women without PCOS.

Docosahexaenoic acid (DHA) intake estimated from a 7-question survey identifies pregnancies most likely to benefit from high-dose DHA supplementation

Two randomized trials found women with low blood docosahexaenoic acid (DHA; an omega 3 fatty acid) had fewer early preterm births (<34 weeks gestation) if they were assigned to high dose DHA supplementation, however, there is currently no capacity for clinicians who care for pregnancies to obtain a blood assessment of DHA. Determining a way to identify women with low DHA intake whose risk could be lowered by high dose DHA supplementation is desired. To determine if assessing DHA intake can identify pregnancies that benefit from high dose DHA supplementation. This secondary analysis used birth data from 1310 pregnant women who completed a 7-question food frequency questionnaire (DHA-FFQ) at 16.8±2.5 weeks gestation that is validated to assess DHA status. They were then randomly assigned to a standard (200mg/day) or high dose (800 or 1000mg/day) DHA supplement for the remainder of pregnancy. Bayesian logistic regressions were fitted for early preterm birth and preterm birth as a function of DHA intake and assigned DHA dose. Participants who consumed less than 150mg/day DHA prior to 20 weeks' gestation (n=810/1310, 58.1%) had a lower Bayesian posterior probability (pp) of early preterm birth if they were assigned to high dose DHA supplementation (1.4% vs 3.9%, pp=0.99). The effect on preterm birth (<37 weeks) was also significant (11.3% vs 14.8%, pp=0.97). The DHA-FFQ can identify pregnancies that will benefit most from high dose DHA supplementation and reduce the risk of preterm birth. The DHA-FFQ is low burden to providers and patients and could be easily implemented in obstetrical practice.

The Unequal Impact of the COVID-19 Pandemic on Infant Health.

The COVID-19 pandemic has taken a large toll on population health and well-being. We examine the consequences of prenatal exposure for infant health, through which the pandemic may have lasting intergenerational effects. We examine multiple pathways by which the pandemic shaped birth outcomes and socioeconomic disparities in these consequences. Analysis of more than 3.5 million birth records in California with universal information on COVID infection among persons giving birth at the time of delivery reveals deep inequalities in infection by education, race/ethnicity, and place-based socioeconomic disadvantage. COVID infection during pregnancy, in turn, predicts a large increase in the probability of preterm birth, by approximately one third. At the population level, a surprising reduction in preterm births during the first months of the pandemic was followed by an increase in preterm births during the surge in COVID infections in the winter of 2021. Whereas the early-pandemic reduction in preterm births benefited primarily highly educated mothers, the increase in preterm births during the winter infection surge was entirely concentrated among mothers with low levels of schooling. The COVID-19 pandemic is expected to exacerbate U.S. inequality in multiple ways. Our findings highlight a particularly enduring pathway: the long-term legacy of prenatal exposure to an unequal pandemic environment.

Elevated serum uric acid level is associated with adverse reproductive outcomes in women with polycystic ovary syndrome undergoing in vitro fertilization or intracytoplasmic sperm injection embryo transfer cycles: a retrospective cohort study

Serum uric acid levels are elevated in polycystic ovary syndrome, however, the relationship between serum uric acid level and reproductive outcomes in women with polycystic ovary syndrome remains unclear. This study aimed to investigate the association between serum uric acid level and the reproductive outcomes in women with polycystic ovary syndrome undergoing invitro fertilization or intracytoplasmic sperm injection embryo transfer cycles. This was a retrospective cohort study performed at a university-affiliated reproductive medicine center. A total of 1903 women with polycystic ovary syndrome undergoing their first invitro fertilization or intracytoplasmic sperm injection embryo transfer cycles between January 2010 and January 2021 were initially included. The trends for reproductive outcomes in polycystic ovary syndrome across quartiles of serum uric acid levels were assessed. A logistic regression analysis was performed to obtain the odds ratios for invitro fertilization outcomes based on the quartiles of serum uric acid with or without adjusting for potential confounding variables. Using generalized additive models, serum uric acid was further treated as its original continuous property to visualize its nonlinear relationship with invitro fertilization outcomes. The live birth rate was the main outcome. After exclusions, a total of 883 women with polycystic ovary syndrome with their first fresh-embryo transfer cycles were included. In quartiles of serum uric acid levels, there was a significant decreasing trend in the live birth rate from the lowest quartile (Q1: 61.8%) to the highest (Q4:45.9%) (Ptrend=.002). The percentage of low birthweight increased from Q1 (22.3%) to Q4 (31.7%) (Ptrend=.049). Compared with those in Q1, women in Q4 showed a significant lower probability of live birth and clinical pregnancy and a higher risk for low birthweight (all P<.05). Both the unadjusted and adjusted generalized additive models indicated that as the serum uric acid level increased, the probability of clinical pregnancy and the live birth rate exhibited an overall decreasing profile, and the risk for low birthweight showed an increasing profile. An elevated serum uric acid level is associated with decreased probabilities of live birth and clinical pregnancy and an increased risk for low birthweight in women with polycystic ovary syndrome. However, these associations may be confounded by other factors and more well-designed studies are needed to confirm these findings in the future.

Endometrial injury for pregnancy following sexual intercourse or intrauterine insemination.

Endometrial injury for pregnancy following sexual intercourse or intrauterine insemination.

Disease Eradication, Infant Mortality, and Fertility Response: Evidence from Malaria Eradication in India

Using a massive malaria eradication program in India during the 1950s as a natural experiment, we examine the effects of disease environment on child health outcomes and fertility. We harmonise a rich dataset on malaria endemicity with fertility histories of women to exploit the cohort level variation in exposure to the program. We find that the program leads to a significant decline in infant and neonatal mortality and leads to a significant increase in the probability of birth during adolescent years in high malaria endemic regions. We confirm that a fall in the mother’s age at first birth in the post-eradication period drives the fertility response.

The effect of paternal and maternal factors on the prognosis of live birth in couples with recurrent pregnancy loss.

Currently, recurrent pregnancy loss (RPL) examinations focus on the woman, although paternal factors are also involved. Men in couples with RPL have higher sperm DNA fragmentation levels than fertile men, but the effect of sperm DNA damage on couple's later prognosis is unknown. Advanced maternal age and obesity are associated with RPL, but paternal lifestyle factors are less studied. Therefore, we aimed to study the associations of couples' lifestyle factors, causes of RPL, and sperm DNA fragmentation with their prognosis of future live birth. This descriptive cohort study comprised 506 couples investigated for RPL at Helsinki University Hospital, Finland, between 2007 and 2016, linked with national health and population registers. The primary outcome was couple's live birth after RPL investigations. Data on couple's background factors, including age, body mass index, smoking, and alcohol use, were collected from medical records. Sperm DNA fragmentation index was analyzed from 211 men using the sperm chromatin dispersion test. The associations between background factors, sperm DNA fragmentation, and cumulative probability of live birth over time were analyzed using cross-tabulations and age-adjusted Cox regression. In all, 352 of 506 couples (69.6%) achieved live birth. Maternal age, unexplained RPL, prolonged pregnancy attempts before investigations, paternal obesity, and maternal smoking were associated with prognosis: unadjusted hazard ratio for couple's live birth for women aged 35-39 vs younger than 30 years was 0.63 (95% confidence interval [CI] 0.47-0.84), and for 40 years or older was 0.36 (95% CI 0.22-0.58). Age-adjusted hazard ratio for unexplained vs explained RPL was 1.39 (95% CI 1.12-1.72), for couple's pregnancy attempt at least 4 years vs less than 2 years was 0.50 (95% CI 0.33-0.76), for paternal body mass index at least 30 kg/m2 vs less than 25 kg/m2 was 0.67 (95% CI 0.46-0.98), and for maternal smoking was 0.71 (95% CI 0.51-0.99). Altogether, 96/135 (71.1%) couples with normal (<15%), 38/60 (63.3%) with intermediate (15-30%), and 11/16 (68.8%) with high sperm DNA fragmentation index achieved live birth (p =0.56). In couples with RPL, prolonged pregnancy attempts, a cause found in RPL examinations, lifestyle factors, and maternal age are negatively associated with their prognosis of future live birth. Sperm DNA fragmentation was not associated, but the number of men with damaged spermatozoa was small. We suggest that clinicians include women and men in RPL counseling because couple's joint lifestyle seems to determine their later prognosis.

Specific lifestyle factors and in vitro fertilization outcomes in Romanian women: a pilot study.

BackgroundInfertility is an important health concern worldwide. Although lifestyle habits and behaviors have been widely reported as predictors of IVF outcomes by previous studies, they have not been reported for Romanian women undergoing IVF. In this regard, our pilot study aimed to begin to address the data gap by assessing lifestyle predictors of in vitro fertilization (IVF) outcomes in Romanian women.Study designOur pilot study included 35 participants who completed a first IVF cycle at a single infertility center. We evaluated individual self-reported lifestyle habits and behaviors as predictors of IVF outcomes, and employed principal component analysis (PCA) to characterize multiple lifestyle habits and behaviors into personal care product (PCP) use, and healthy diet and physical activity patterns as predictors of IVF outcomes.ResultsOur PCA analysis showed that greater use of PCPs was associated with lower probabilities of pregnancy (RR: 0.92, 95% CI [0.87–0.98]) and live birth (RR: 0.94, 95% CI [0.88–1.01]) while, the healthy dietary habits and physical activity were associated with a higher likelihood of pregnancy, although without statistical significance (RR: 1.10, 95% CI [0.93–1.30]).ConclusionsIn this pilot study we identified associations between IVF outcomes among Romanian women and certain lifestyle habits and behaviors including stress, diet and physical activity, and certain PCP use. We also estimated the joint effects of multiple lifestyle factors using PCA and found that PCP use, healthy dietary habits and physical activity were associated with IVF outcomes.

Anti-Müllerian Hormone and Follicle-Stimulating Hormone Are Poor Independent Predictors of Live Birth After Assisted Reproductive Technology.

To query if anti-Müllerian hormone (AMH) and/or follicle-stimulating hormone (FSH) predict live birth at the University of Colorado Advanced Reproductive Medicine (CU ARM). This was a retrospective analysis using the Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System database at CU ARM from 2017 to 2019 to identify the pregnancy outcomes of the initial fresh or frozen embryo transfer (FET) and their corresponding AMH and FSH. Fisher's exact tests were used to identify differences in pregnancy outcome by age group, and area under the receiver operator characteristic curves was used to quantify live birth prediction. A total of 1083 records from 557 patients were reviewed. After only including the first autologous transfer, 270 cycles were analyzed. Overall live birth (L/B) rate was 58.15% (157/270), which declined with increasing age group (p ≤ 0.01). Although AMH significantly decreased with increasing age (p < 0.001), it was not associated with pregnancy outcome (3.54ng/mL vs. 3.41ng/mL, p = 0.56); this relationship was unchanged after controlling for age in logistic regression models (p = 0.52). FSH was also not significantly related to pregnancy outcome (7.00IU/L vs 6.00IU/L, p = 0.15), and this relationship did not change after controlling for age (p = 0.61). Using AUC, the only variable predictive of live birth was age (p = 0.002). AMH and FSH are not associated with the probability of live birth. Only age was significantly associated with live birth in this series. AMH and FSH should therefore be used cautiously when counseling patients about ART outcomes.

Good predictors for the fixation probability on complex networks of multi-player games using territorial interactions

In 2012 Broom and Rychtar developed a new framework to consider the evolution of a population over a non-homogeneous underlying structure, where fitness depends upon multiplayer interactions amongst the individuals within the population played in groups of various sizes (including one). This included the independent model, and as a special case the territorial raider model, which has been considered in a series of subsequent papers. Here individuals are based upon the vertex of a graph but move to interact with their neighbours, sometimes meeting in large groups. The most important single property of such populations is the fixation probability, the probability of a single mutant completely replacing the existing population. In a recent paper we considered the fixation probability for the Birth Death Birth (BDB) dynamics for three games, a Public Goods game, the Hawk–Dove game and for fixed fitnesses for a large number of randomly generated graphs, in particular seeing if important underlying graph properties could be used as predictors. We found two good predictors, temperature and mean group size, but some interesting and unusual features for one type of graph, Barabasi–Albert graphs. In this paper we use a regression analysis to investigate (the usual) three alternative evolutionary dynamics (BDD, DBB, DBD) in addition to the original BDB. In particular, we find that the dynamics split into two pairs, BDB/DBD and BDD/DBB, each of which give essentially the same results and found a good fit to the data using a quadratic regression involving the above two variables. Further we find that temperature is the most important predictor for the Hawk–Dove game, whilst for the Public Goods game the group size also plays a key role, and is more important than the temperature for the BDD/DBB dynamics.

IN VITRO FERTILIZATION OUTCOMES AMONG WOMEN WITH RECURRENT PREGNANCY LOSS IN THE UNITED STATES

There is controversy surrounding the utility of in vitro fertilization (IVF) and preimplantation genetic testing for aneuploidy (PGT-A) as a treatment for women with recurrent pregnancy loss (RPL). We hypothesized that in women with RPL, the addition of PGT-A would improve the probability of live birth per cycle start in the first embryo transfer following retrieval. This study aims to evaluate the impact of PGT-A on IVF outcomes among women with RPL in the United States (US).

What to advise to patients with only one good quality blastocyst, PGT-A or not? Outcomes of 2064 cycles

PurposeTo evaluate whether preimplantation genetic testing for aneuploidy (PGT-A) is beneficial for patients who have only one blastocyst available for biopsy or transfer.MethodsThis retrospective study was based on 1126 single blastocyst PGT-A and 938 non-PGT-A cycles, a total of 2064 ART cycles which resulted in a single good quality blastocyst in women between 20 and 45 years old. The PGT-A group had 225 single euploid embryo transfer cycles and the non-PGT-A group had 938 single blastocyst embryo transfer cycles.ResultsIn the generalized linear mixed model (GLMM), female age and PGT-A variables were found to be significant variables on pregnancy outcomes. In the PGT-A cases, regardless of the effect of other variables, the probabilities of clinical pregnancy and live birth were found to be 3.907 and 3.448 fold higher respectively than in the non-PGT-A cases (p < 0.001). In non PGT-A cases, the probability of a total pregnancy loss was found to be 1.943 fold higher (p = 0.013).ConclusionPGT-A in the presence of a single blastocyst significantly increases clinical pregnancy and live birth rates and decreases total pregnancy losses regardless of age. In addition, aneuploid embryo transfer cancelations prevent ineffective and potentially risky transfers.

Racial/ethnic disparities in phthalate metabolite mixtures and risk of preterm birth: A pooled study of 16 US cohorts

BACKGROUND AND AIM. Environmental phthalate exposure is ubiquitous in pregnancy and may be a risk factor for preterm delivery. In the United States (US), large racial/ethnic disparities in phthalate exposure may be an important contributor to the racial/ethnic disparities in preterm birth. Utilizing the largest study of phthalates and preterm birth to date, we 1) investigated racial/ethnic disparities in phthalate exposure and 2) estimated how racial/ethnic disparities in preterm birth might improve by equitably reducing phthalate exposure. METHODS. We pooled individual-level data from 16 US cohorts (N=6,045) on 9 prenatal urinary phthalate metabolites. We categorized participant race/ethnicity as non-Hispanic white (43%), non-Hispanic Black (13%), Hispanic/Latina (38%), or Other (5%; based on sparsity of sub-categories). We investigated confounder-adjusted differences in urinary phthalate metabolite concentrations by maternal race/ethnicity. We used g-computation to estimate changes in preterm birth by race/ethnicity after simultaneous, racial/ethnic-specific reductions in the concentration of all 9 phthalate metabolites. Our hypothetical intervention eliminated racial/ethnic disparities in the distributions of metabolite concentrations. RESULTS. For 8 of the 9 phthalate metabolites, concentrations were highest among non-Hispanic Black participants and lowest among non-Hispanic whites. Covariate-adjusted differences in metabolite concentrations were most pronounced for monoethyl phthalate and mono-isobutyl phthalate, which were 143% (95% confidence interval [95CI]: 114%, 175%) and 80% (95CI: 66%, 95%) higher among non-Hispanic Black compared to non-Hispanic white participants, respectively. The hypothetical intervention to simultaneously reduce concentrations of metabolites by race/ethnicity, principally among non-white racial/ethnic groups, showed significant reductions in preterm birth. For non-Hispanic Black participants, the pre- and post-intervention probability of preterm birth was 117 (95CI: 94, 141) and 88 (95CI: 61, 118) preterm per 1,000 live births, respectively, representing a relative reduction of 25% (95CI: 16%, 35%). CONCLUSIONS. Considerable differences in exposure to phthalates could play an important role in the racial/ethnic disparities in preterm birth within the US.

Temporal changes in the probability of live birth among female survivors of childhood cancer: a population-based adult life after childhood cancer in Scandinavia (ALiCCS) study in five Nordic countries

Temporal changes in the probability of live birth among female survivors of childhood cancer: a population-based adult life after childhood cancer in Scandinavia (ALiCCS) study in five Nordic countries

The effect of frozen embryo transfer regimen on the association between serum progesterone and live birth: a multicentre prospective cohort study (ProFET).

What is the association between serum progesterone levels on the day of frozen embryo transfer (FET) and the probability of live birth in women undergoing different FET regimens? Overall, serum progesterone levels <7.8 ng/ml were associated with reduced odds of live birth, although the association between serum progesterone levels and the probability of live birth appeared to vary according to the route of progesterone administration. Progesterone is essential for pregnancy success. A recent systematic review showed that in FET cycles using vaginal progesterone for endometrial preparation, lower serum progesterone levels (<10 ng/ml) were associated with a reduction in live birth rates and higher chance of miscarriage. However, there was uncertainty about the association between serum progesterone levels and treatment outcomes in natural cycle FET (NC-FET) and HRT-FET using non-vaginal routes of progesterone administration. This was a multicentre (n = 8) prospective cohort study conducted in the UK between January 2020 and February 2021. We included women having NC-FET or HRT-FET treatment with progesterone administration by any available route. Women underwent venepuncture on the day of embryo transfer. Participants and clinical personnel were blinded to the serum progesterone levels. We conducted unadjusted and multivariable logistic regression analyses to investigate the association between serum progesterone levels on the day of FET and treatment outcomes according to the type of cycle and route of exogenous progesterone administration. Our primary outcome was the live birth rate per participant. We studied a total of 402 women. The mean (SD) serum progesterone level was 14.9 (7.5) ng/ml. Overall, the mean adjusted probability of live birth increased non-linearly from 37.6% (95% CI 26.3-48.9%) to 45.5% (95% CI 32.1-58.9%) as serum progesterone rose between the 10th (7.8 ng/ml) and 90th (24.0 ng/ml) centiles. In comparison to participants whose serum progesterone level was ≥7.8 ng/ml, those with lower progesterone (<7.8 ng/ml, 10th centile) experienced fewer live births (28.2% versus 40.0%, adjusted odds ratio [aOR] 0.41, 95% CI 0.18-0.91, P = 0.028), lower odds of clinical pregnancy (30.8% versus 45.1%, aOR 0.36, 95% CI 0.16-0.79, P = 0.011) and a trend towards increased odds of miscarriage (42.1% versus 28.7%, aOR 2.58, 95% CI 0.88-7.62, P = 0.086). In women receiving vaginal progesterone, the mean adjusted probability of live birth increased as serum progesterone levels rose, whereas women having exclusively subcutaneous progesterone experienced a reduction in the mean probability of live birth as progesterone levels rose beyond 16.3 ng/ml. The combination of vaginal and subcutaneous routes appeared to exert little impact upon the mean probability of live birth in relation to serum progesterone levels. The final sample size was smaller than originally planned, although our study was adequately powered to confidently identify a difference in live birth between optimal and inadequate progesterone levels. Furthermore, our cohort did not include women receiving oral or rectal progestogens. Our results corroborate existing evidence suggesting that lower serum progesterone levels hinder FET success. However, the relationship between serum progesterone and the probability of live birth appears to be non-linear in women receiving exclusively subcutaneous progesterone, suggesting that in this subgroup of women, high serum progesterone may also be detrimental to treatment success. This work was supported by CARE Fertility and a doctoral research fellowship (awarded to P.M.) by the Tommy's Charity and the University of Birmingham. M.J.P. is supported by the NIHR Birmingham Biomedical Research Centre. S.F. is a minor shareholder of CARE Fertility but has no financial or other interest with progesterone testing or manufacturing companies. P.L. reports personal fees from Pharmasure, outside the submitted work. G.P. reports personal fees from Besins Healthcare, outside the submitted work. M.W. reports personal fees from Ferring Pharmaceuticals, outside the submitted work. The remaining authors have no conflict of interest to declare. ClinicalTrials.gov: NCT04170517.

PROJECT METHOD IN THE COURSE “FUNDAMENTALS OF ANTHROPOLOGY, BIOLOGY AND HUMAN GENETICS”: FORMATION OF PROFESSIONAL COMPETENCES IN WOULD-BE TEACHERS OF BIOLOGY AND HEALTH STUDIES

The paper studies the methodological aspects of applying the project method by students majoring in 014. Secondary education in the course "Fundamentals of Anthropology, Biology and Human Genetics" and the formation of professional competencies of would-be teachers of Biology and Human Health in the field of Genetics. It is shown that the use of project technology for the study of the course of human genetics is only possible with high professionalism of the teacher. The teacher must thoroughly develop methods of working with the project, formulate clear instructions for its implementation, evaluation criteria, provide methodological support, and act as a facilitator during the project. It is demonstrated that project work on human genetics is a holistic structural didactic unit that has its purpose, content, and a problem task, solution to which requires performing a series of structured sub-tasks.&#x0D; It is ascertained that the student effective work on the project includes stages of searching for scientific literature on methodological aspects of the role of clinical and genealogical method in human genetic research and genealogical analysis; collecting data on the family on the basis of research (starting with proband); formation of a legend on this basis and formulation of a task to determine the probability of occurrence in the family of a proband of children with the studied feature; compilation of a pedigree chart; analysis of the constructed pedigree; determining the type of inheritance of the studied trait; calculating the probability of birth in the family of proband offspring with the studied trait.&#x0D; It was found that on competing the project 57.1% of students achieved a high level of formation of the general and special competencies in the future specialty, 17.9% - intermediate level, 21.4% - sufficient, and 3.6% - low level. The research proves the effectiveness of project method in the study of the course "Fundamentals of Anthropology, Biology and Human Genetics" for the formation of general and special competencies in would-be teachers of biology and human health in the field of genetics. Not only the level of motivation of students to obtain genetic knowledge increased, but also their interest in the project, as such work helps to expand knowledge about close and distant relatives, family relationships, increase respect for their own family, development of logical thinking, and creative thinking.

Is Frozen Embryo Transfer the New Norm in IVF?

Frozen embryo transfer is an established, highly successful technology in Assisted Reproductive Technologies. Its use as a part of a freeze only strategy is associated with a higher probability of live birth in high responders and a decrease incidence of ovarian hyperstimulation syndrome (OHSS). Its use in normal responders, maintains the probability of live birth compared to fresh embryo transfer and decreases the incidence of OHSS. Obstetric n neonatal outcomes in frozen as compared to fresh embryo transfer cycles are characterized by a decreased incidence of monozygotic twinning, of ectopic pregnancy, of small for gestational age babies, of premature labour, of antepartum hemorrhage and of perinatal mortality. On the other hand, an increased incidence of pregnancy induced hypertension, has been observed in frozen as compared to fresh embryo transfer cycles. This, however, appears to be associated with the absence of corpus luteum during endometrium preparation for embryo transfer, as is the case in frozen embryo transfer cycles using hormonal replacement. Overall, the increased efficacy and a safety present, if fresh embryo transfer following ovarian stimulation is avoided, redefine what should be the norm in modern in-vitro fertilization practice.

Predicting cumulative live birth for couples beginning their second complete cycle of in vitro fertilization treatment.

STUDY QUESTIONCan we develop an IVF prediction model to estimate individualized chances of a live birth over multiple complete cycles of IVF in couples embarking on their second complete cycle of treatment?SUMMARY ANSWERYes, our prediction model can estimate individualized chances of cumulative live birth over three additional complete cycles of IVF.WHAT IS KNOWN ALREADYAfter the completion of a first complete cycle of IVF, couples who are unsuccessful may choose to undergo further treatment to have their first child, while those who have had a live birth may decide to have more children. Existing prediction models can estimate the overall chances of success in couples before commencing IVF but are unable to revise these chances on the basis of the couple’s response to a first treatment cycle in terms of the number of eggs retrieved and pregnancy outcome. This makes it difficult for couples to plan and prepare emotionally and financially for the next step in their treatment.STUDY DESIGN, SIZE, DURATIONFor model development, a population-based cohort was used of 49 314 women who started their second cycle of IVF including ICSI in the UK from 1999 to 2008 using their own oocytes and their partners’ sperm. External validation was performed on data from 39 442 women who underwent their second cycle from 2010 to 2016.PARTICIPANTS/MATERIALS, SETTING, METHODSData about all UK IVF treatments were obtained from the Human Fertilisation and Embryology Authority (HFEA) database. Using a discrete time logistic regression model, we predicted the cumulative probability of live birth from the second up to and including the fourth complete cycles of IVF. Inverse probability weighting was used to account for treatment discontinuation. Discrimination was assessed using c-statistic and calibration was assessed using calibration-in-the-large and calibration slope.MAIN RESULTS AND THE ROLE OF CHANCEFollowing exclusions, 49 314 women with 73 053 complete cycles were included. 12 408 (25.2%) had a live birth resulting from their second complete cycle. Cumulatively, 17 394 (35.3%) had a live birth over complete cycles two to four. The model showed moderate discriminative ability (c-statistic: 0.65, 95% CI: 0.64 to 0.65) and evidence of overprediction (calibration-in-the-large = −0.08) and overfitting (calibration slope 0.85, 95% CI: 0.81 to 0.88) in the validation cohort. However, after recalibration the fit was much improved. The recalibrated model identified the following key predictors of live birth: female age (38 versus 32 years—adjusted odds ratio: 0.59, 95% CI: 0.57 to 0.62), number of eggs retrieved in the first complete cycle (12 versus 4 eggs; 1.34, 1.30 to 1.37) and outcome of the first complete cycle (live birth versus no pregnancy; 1.78, 1.66 to 1.91; live birth versus pregnancy loss; 1.29, 1.23 to 1.36). As an example, a 32-year-old with 2 years of non-tubal infertility who had 12 eggs retrieved from her first stimulation and had a live birth during her first complete cycle has a 46% chance of having a further live birth from the second complete cycle of IVF and an 81% chance over a further three cycles.LIMITATIONS, REASONS FOR CAUTIONThe developed model was updated using validation data that was 6 to 12 years old. IVF practice continues to evolve over time, which may affect the accuracy of predictions from the model. We were unable to adjust for some potentially important predictors, e.g. BMI, smoking and alcohol intake in women, as well as measures of ovarian reserve such as antral follicle count. These were not available in the linked HFEA dataset.WIDER IMPLICATIONS OF THE FINDINGSBy appropriately adjusting for couples who discontinue treatment, our novel prediction model will provide more realistic chances of live birth in couples starting a second complete cycle of IVF. Clinicians can use these predictions to inform discussion with couples who wish to plan ahead. This prediction tool will enable couples to prepare emotionally, financially and logistically for IVF treatment.STUDY FUNDING/COMPETING INTEREST(S)This study was supported by an Elphinstone scholarship scheme at the University of Aberdeen and Aberdeen Fertility Centre, University of Aberdeen. The authors have no conflict of interest.TRIAL REGISTRATION NUMBERN/A.

Social Investment Policies and Childbearing Across 20 Countries: Longitudinal and Micro-Level Analyses

This study analyses the influence of family policies on women’s first and second births in 20 countries over the period 1995 to 2007. Welfare states have shifted towards social investment policies, yet family policy–fertility research has not explicitly considered this development. We distinguish between social investment-oriented and passive support that families may receive upon the birth of a child and consider changes in policies over time. These indicators are merged with fertility histories provided by harmonized individual-level data, and we use time-conditioned, fixed effects linear probability models. We find higher social investment-oriented support to be correlated with increased first birth probabilities, in contrast to passive family support. First birth probabilities particularly declined with higher passive family support for women over age 30, which points to a potential increase in childlessness. Social investment-oriented support is positively related to first and second births particularly for lower-educated women and has no relationship to childbirth for highly educated women, countering the Matthew-effect assumptions about social investment policies. Passive support is negatively related to second births for post-secondary educated women and those who are studying. Family policies that support women’s employment and labour market attachment are positively linked to family expansion and these policies minimize educational differences in childbearing.