Condições de nascimento e fatores gestacionais associados, antes e durante a pandemia da covid-19, no distrito de nampula­ moçambique / Birth conditions and associated gestational factors, before and during the covid-19 pandemic, in the district of Nampula - Mozambique

ALBERTO, Rapieque José, M.Sc., Universidade Federal de Viçosa, março de 2023. Condições de nascimento e fatores gestacionais associados, antes e durante a pandemia da COVID-19, no distrito de Nampula­Moçambique. Orientadora Sílvia Eloiza Priore. Coorientadores: Dayane de Castro Morais, Sylvia do Carmo Castro Franceschini e Amélia Suzana Eduardo Mandane. Introdução: O peso ao nascer é um indicador com repercussão na saúde e sobrevida infantil, podendo aumentar o risco de morbimortalidade no primeiro ano de vida quando este for inferior a 2500 gramas. Durante a pandemia da COVID-19, o setor de saúde viu se obrigado a ajustar o modelo de assistência às gestantes, afetando adversamente a saúde materna e os resultados perinatais, por conta da adoção de medidas restritivas para contenção da propagação do vírus. Portanto, o estudo objetivou avaliar as condições de nascimento e os fatores gestacionais associados antes e durante a pandemia da COVID-19 no distrito de Nampula-Moçambique. Metodologia: trata-se de um estudo transversal retrospetivo, realizado com dados obtidos nos livros de registo das consultas pré-natal e maternidade, referente ao mês de dezembro dos anos de 2019 (pré pandêmico), 2020 (fase aguda) e de 2021 (fase amena) em dez centros de saúde do distrito de Nampula. Nas análises a fase pandêmica foi tida como única porque a variável dependente (peso ao nascer) não apresentou diferenças (p>0,05) quando comparado os anos de 2020 e 2021. Foi utilizado o Software Statistical Packege for the Social Sciences (SPSS) versão 20.0. A distribuição das variáveis foi avaliada conforme teste Kolmogorov Smirnov e a análise descritiva foi por mediana (valor mínimo e máximo). Para comparar as variáveis independentes entre os grupos foi aplicada o Teste Kruskal Wallis com post hoc de Dunn. A associação foi realizada pelo teste Qui-quadrado de Person (χ 2) e teste exato de Fisher com tabela de dupla entrada. A regressão logística binaria foi utilizada para avaliar a associação entre o peso ao nascer e as variáveis preditoras que apresentaram p<0,05)…

ALBERTO, Rapieque José, M.Sc., Universidade Federal de Viçosa, March 2023. Conditions of birth and associated gestational factors, before and during the COVID-19 pandemic, in the district of Nampula, Mozambique. Advisor: Sílvia Eloiza Priore. Co-Advisor: Dayane de Castro Morais, Sylvia do Carmo Castro Franceschini and Amélia Suzana Eduardo Mandane. Introduction: Birth weight is an indicator with consequences on infant health and survival, it may increase the risk of morbidity and mortality in the first year of life when it is below 2.5 kilograms. During the COVID-19 pandemic, the health sector had to adjust the care model for pregnant women, which had a negative impact on maternal health and perinatal outcomes because of the implementation of restrictive measures to contain the spread of the virus. Therefore, this study aims to evaluate the birth conditions and associated gestational factors before and during the COVID-19 pandemic in the district of Nampula, Mozambique. Methodology: This is a retrospective cross-sectional study, carried out with data obtained from the records of prenatal and maternity consultations, referring to the month of December of the years 2019 (pre-pandemic), 2020 (acute phase) and 2021 (mild phase) in ten health canters in Nampula district. In the analysis, the pandemic phase was considered the only one because the dependent variable (birth weight) did not differ (p>0.05) when comparing the years 2020 and 2021. Was used The Statistical Package Software for the Social Sciences (SPSS) version 20.0. The distribution of variables was evaluated according to the Kolmogorov-Smirnov test; the descriptive analysis was by median (minimum and maximum value). To compare the independent variables between the groups, the Kruskal Wallis Test with Dunn's post-hoc was applied. The association was performed using Person's chi-square test (χ2) and Fisher's exact test with a double entry table. Binary logistic regression was used to assess the association between birth weight and the predictor variables that presented p<0.05)…

Trends in Pregnancy Rates in an Urban Adolescent Clinic Before and During the COVID-19 Pandemic.

We examined COVID-19 pandemic-related changes on reproductive health care delivery and pregnancy rates in an adolescent clinic. Through a retrospective data collection as part of quality improvement project, we compared the number of pregnancies, visit percentages for newly diagnosed pregnancies, and number/percentage of long acting reversible contraception (LARC) visits. The percentage of visits for newly diagnosed pregnancies during the first 3 months of the COVID-19 pandemic (April-June 2020) increased significantly relative to pre-pandemic percentages while the absolute number of new pregnancies only trended upward. Over the same timeframe, the total number of LARC visits decreased, although they consisted of a higher percentage of all in-person visits than pre-pandemic. After the first few months of the pandemic, these values returned to pre-pandemic levels. The substantial increase in the rate of new pregnancies during the first 3 to 6 months of the COVID-19 pandemic demonstrates the importance of prioritizing access to reproductive health care services for adolescents and young adults.

Characterization of an artificial intelligence model for ranking static images of blastocyst stage embryos.

OBJECTIVE: To perform a series of analyses characterizing an artificial intelligence (AI) model for ranking blastocyst-stage embryos. The primary objective was to evaluate the benefit of the model for predicting clinical pregnancy, whereas the secondary objective was to identify limitations that may impact clinical use. DESIGN: Retrospective study. SETTING: Consortium of 11 assisted reproductive technology centers in the United States. PATIENT(S): Static images of 5,923 transferred blastocysts and 2,614 nontransferred aneuploid blastocysts. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Prediction of clinical pregnancy (fetal heartbeat). RESULT(S): The area under the curve of the AI model ranged from 0.6 to 0.7 and outperformed manual morphology grading overall and on a per-site basis. A bootstrapped study predicted improved pregnancy rates between +5% and +12% per site using AI compared with manual grading using an inverted microscope. One site that used a low-magnification stereo zoom microscope did not show predicted improvement with the AI. Visualization techniques and attribution algorithms revealed that the features learned by the AI model largely overlap with the features of manual grading systems. Two sources of bias relating to the type of microscope and presence of embryo holding micropipettes were identified and mitigated. The analysis of AI scores in relation to pregnancy rates showed that score differences of ≥0.1 (10%) correspond with improved pregnancy rates, whereas score differences of <0.1 may not be clinically meaningful. CONCLUSION(S): This study demonstrates the potential of AI for ranking blastocyst stage embryos and highlights potential limitations related to image quality, bias, and granularity of scores.

Testicular sperm characteristics in men with nonobstructive azoospermia and their impact on intracytoplasmic sperm injection outcome.

OBJECTIVE: To report fertilization and clinical pregnancy rates based on sperm characteristics at the time of intracytoplasmic sperm injection (ICSI) in men with nonobstructive azoospermia (NOA) following microdissection testicular sperm extraction (mTESE). DESIGN: Retrospective cohort. SETTING: Tertiary hospital. PATIENT(S): Men with NOA undergoing mTESE between 2013 and 2016 who had successful sperm retrieval and subsequent spermatozoa available for ICSI. INTERVENTION(S): Sperm characteristic assessment. MAIN OUTCOME MEASURE(S): Fertilization and clinical pregnancy rates. RESULT(S): One hundred ninety-eight men with NOA and successful mTESE were included. The mean ages of the patients and their partners were 35 ± 8 and 31 ± 5 years, respectively. The overall fertilization rate was 44%, and the clinical pregnancy rate was 38%. The absence of twitching sperm motility and the presence of an acrosome defect were associated with decreased fertilization and clinical pregnancy rates on univariable analysis. On multivariable analysis, the presence of motility was associated with higher fertilization rates and greater odds of clinical pregnancy (odds ratio, 4.37; 95% confidence interval, 1.61-11.85). An abnormal acrosome was associated with reduced odds of pregnancy (odds ratio, 0.40; 95% confidence interval, 0.18-0.85). No specific anomaly or combination of sperm abnormalities precluded fertilization or clinical pregnancy with ICSI. CONCLUSION(S): To our knowledge, this is the first comprehensive study evaluating the importance of sperm characteristics and their impact on ICSI outcomes in men with NOA. The results suggest that no specific defect, including the use of nonmotile testicular spermatozoa, precluded a chance of clinical pregnancy. The study evaluated sperm characteristics at the time of ICSI injection; initial evaluation at the time of retrieval may differ significantly from that of spermatozoa selected for ICSI.

Analysis on clinical association of uterine scar diverticulum with subsequent infertility in patients underwent cesarean section.

ABSTRACT: To evaluate the relationship between uterine cesarean scar diverticulum (CSD) and subsequent infertility in patients who underwent cesarean section, and determine the effects of pelvic fluid-releasing inflammations on infertility.A retrospective analysis was designed among patients with CSD who were admitted to our hospital from January 1, 2018 to December 31, 2019. A total of 60 patients with CSD and uterine fibroids or benign ovarian tumors who underwent cesarean section were included, and divided into the CSD group and control group. Baseline characteristics of all patients were collected, and the pelvic adhesion scores and the percents of tubal patency were evaluated. Furthermore, the postoperative clinical outcomes were followed up. The levels of inflammatory factors in pelvic fluid were tested using Elisa kits.Preoperative data indicated that the size of the uterine scar diverticulum was (1.68 ±â€Š0.52) cm, the pelvic adhesion scores were higher in CSD group than control group (4.67 ±â€Š0.90 vs 0.47 ±â€Š0.90, P < .05), and 21 of 30 patients with unobstructed fallopian tubes. The levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-6 in patients with CSD were obviously higher than control group (P < .05). After the follow-up, the data displayed that no CSD was found in all patients, the time of menstrual period in patients with CSD was shortened to 7.80 ±â€Š1.27 days, and the myometrial thickness at uterine scar was significantly increased (P < .05). Additionally, the pregnancy rate was increased, and 12 of 30 patients were repregnant. Correlation analysis showed that the levels of inflammatory factors (tumor necrosis factor-α, interleukin-1ß, interleukin-6), the size of uterine scar diverticulum, and the myometrial thickness at uterine scar were significantly correlated with subsequent infertility (r = 0.307, 0.083, 0.147, 0.405, 0.291, P < .05).Uterine scar diverticulum repair could improve menstrual prolongation, increased the thickness of myometrium and repregnant rate. Subsequent infertility was positively correlated with uterine scar diverticulum and the levels of inflammatory factors.

Trends and factors related to adolescent pregnancies: an incidence trend and conditional inference trees analysis of northern Nicaragua demographic surveillance data.

BACKGROUND: We aimed to identify the 2001-2013 incidence trend, and characteristics associated with adolescent pregnancies reported by 20-24-year-old women. METHODS: A retrospective analysis of the Cuatro Santos Northern Nicaragua Health and Demographic Surveillance 2004-2014 data on women aged 15-19 and 20-24. To calculate adolescent birth and pregnancy rates, we used the first live birth at ages 10-14 and 15-19 years reported by women aged 15-19 and 20-24 years, respectively, along with estimates of annual incidence rates reported by women aged 20-24 years. We conducted conditional inference tree analyses using 52 variables to identify characteristics associated with adolescent pregnancies. RESULTS: The number of first live births reported by women aged 20-24 years was 361 during the study period. Adolescent pregnancies and live births decreased from 2004 to 2009 and thereafter increased up to 2014. The adolescent pregnancy incidence (persons-years) trend dropped from 2001 (75.1 per 1000) to 2007 (27.2 per 1000), followed by a steep upward trend from 2007 to 2008 (19.1 per 1000) that increased in 2013 (26.5 per 1000). Associated factors with adolescent pregnancy were living in low-education households, where most adults in the household were working, and high proportion of adolescent pregnancies in the local community. Wealth was not linked to teenage pregnancies. CONCLUSIONS: Interventions to prevent adolescent pregnancy are imperative and must bear into account the context that influences the culture of early motherhood and lead to socioeconomic and health gains in resource-poor settings.

Defining recurrent implantation failure: a profusion of confusion or simply an illusion?

Recurrent implantation failure (RIF) is a poorly defined clinical scenario marked by failure to achieve pregnancy after multiple embryo transfers. The causes and definitions of implantation failure are heterogeneous, posing limitations on study design as well as the interpretation and application of findings. Recent studies suggest a novel, personalized approach to defining RIF. Here, we review the implantation physiology and definitions of the implantation rate, failure, and RIF.

A review of the pathophysiology of recurrent implantation failure.

Implantation is a critical step in human reproduction. The success of this step is dependent on a competent blastocyst, receptive endometrium, and successful cross talk between the embryonic and maternal interfaces. Recurrent implantation failure is the lack of implantation after the transfer of several embryo transfers. As the success of in vitro fertilization has increased and failures have become more unacceptable for patients and providers, the literature on recurrent implantation failure has increased. While this clinical phenomenon is often encountered, there is not a universally agreed-on definition-something addressed in an earlier portion of this Views and Reviews. Implantation failure can result from several different factors. In this review, we discuss factors including the maternal immune system, genetics of the embryo and parents, anatomic factors, hematologic factors, reproductive tract microbiome, and endocrine milieu, which factors into embryo and endometrial synchrony. These potential causes are at various stages of research and not all have clear implications or immediately apparent treatment.

Relationship between semen regurgitation and pregnancy rates with intrauterine insemination.

OBJECTIVE: To evaluate the relationship between semen regurgitation and intrauterine insemination (IUI) outcomes. We hypothesized that clinical pregnancy rates and live birth rates would be reduced when regurgitation occurred. DESIGN: Retrospective cohort study. SETTING: A university-based reproductive endocrinology and infertility clinic. PATIENT(S): Retrospective review of 1,957 IUI cycles performed on 660 patients between July 2007 and May 2012. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was live birth. Secondary outcomes were positive serum pregnancy result and clinical pregnancy. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a cluster-weighted generalized estimating equations method to estimate modified Poisson regression models with robust standard errors to account for multiple IUI cycles in the same patient. RESULT(S): Live birth rates were similar in IUI cycles with and without regurgitation (6.3% vs. 6.8%, respectively, RR = 0.82, 95% CI [0.53-1.26]). Clinical pregnancy rates in the presence or absence of regurgitation were 10.5% vs. 10.0% (RR = 0.99, 95% CI [0.73-1.35]). Positive serum pregnancy tests after IUI did not differ by regurgitation status (15.0% vs. 15.4%, RR = 0.97, 95% CI [0.75-1.24]). Results were unchanged when adjusted for covariates (age, race and ethnicity, body mass index, duration of infertility, medication, infertility diagnosis, total motile count, and method of sperm preparation). CONCLUSION(S): The presence of regurgitation during the IUI procedure is not related to pregnancy outcome.

Serum luteal phase progesterone in women undergoing frozen embryo transfer in assisted conception: a systematic review and meta-analysis.

OBJECTIVE: To investigate the association between luteal serum progesterone levels and frozen embryo transfer (FET) outcomes. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women undergoing FET. INTERVENTION(S): We conducted electronic searches of MEDLINE, PubMed, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and grey literature (not widely available) from inception to March 2021 to identify cohort studies in which the serum luteal progesterone level was measured around the time of FET. MAIN OUTCOME MEASURE(S): Ongoing pregnancy or live birth rate, clinical pregnancy rate, and miscarriage rate. RESULT(S): Among the studies analyzing serum progesterone level thresholds <10 ng/mL, a higher serum progesterone level was associated with increased rates of ongoing pregnancy or live birth (relative risk [RR] 1.47, 95% confidence interval [CI] 1.28 to 1.70), higher chance of clinical pregnancy (RR 1.31, 95% CI 1.16 to 1.49), and lower risk of miscarriage (RR 0.62, 95% CI 0.50 to 0.77) in cycles using exclusively vaginal progesterone and blastocyst embryos. There was uncertainty about whether progesterone thresholds ≥10 ng/mL were associated with FET outcomes in sensitivity analyses including all studies, owing to high interstudy heterogeneity and wide CIs. CONCLUSION(S): Our findings indicate that there may be a minimum clinically important luteal serum concentration of progesterone required to ensure an optimal endocrine milieu during embryo implantation and early pregnancy after FET treatment. Future clinical trials are required to assess whether administering higher-dose luteal phase support improves outcomes in women with a low serum progesterone level at the time of FET. PROSPERO NUMBER: CRD42019157071.

Influence of lactation number and parity on milk yield of Saanen goat's breed / [Influência do número de lactação e paridade na produção de leite da raça de cabras Saanen]

The aim of this research was to determine the influence of lactation number and parity on milk yield of Saanen goat's breed. It has been concluded that milk yield was higher for goats that had given birth to twins and three kids than for goats that had given birth to a single kid (P<0.05). The longevity has a great positive impact on production, given that goats in the fifth lactation produced more milk than goats in first or second lactation (P<0.05), while goats in the sixth lactation still produced more milk than goats in first lactation (P<0.05). During the period from 2014- 2019, the research was conducted on a farm of multiparous Saanen goats in Vojvodina (northern part of Serbia). In the observed period, the farm had between 350 and 400 goats per milking, and the research included a total of 1,628 concluded lactations, within which the first lactations were the most 484, then the second 381. According to the number of lactations, goats were grouped into classes from one to seven and from one to three for parity. By comparing each individual lactation, it was determined that in first lactation goats produced significantly lower milk than goats in the rest lactations(P<0.05), except the seventh. Research has shown that lactation number has a significant influence on milk yield (P=0.00). Increasing the fertility of goats significantly affects the production capacity of dairy goats, since does with a larger number of kids in the litter had a significantly higher milk production (P<0.05). Due to the larger number of kids in the litter, milk production also increases. Likewise, it is assumed that the increase in milk yield of goats with two and three kids is a consequence of a larger placenta, i.e. stronger lactogenic activity during pregnancy.(AU)

O objetivo desta pesquisa foi determinar a influência do número de lactações e da paridade na produção de leite da raça de cabras Saanen. Concluiu-se que a produção de leite era maior para caprinos que haviam dado à luz gêmeos e três cordeiros do que para caprinos que haviam dado à luz um único cordeiro (P<0,05). A longevidade tem um grande impacto positivo na produção, dado que as cabras na quinta lactação produziram mais leite do que as cabras na primeira ou segunda lactação (P<0,05), enquanto as cabras na sexta lactação ainda produziram mais leite do que as cabras na primeira lactação (P<0,05). Durante o período de 2014- 2019, a pesquisa foi realizada numa fazenda de cabras Saanen multipares em Voivodina (parte norte da Sérvia). No período observado, a fazenda tinha entre 350 e 400 cabras por ordenha, e a pesquisa incluiu um total de 1.628 lactações concluídas, dentro das quais as primeiras lactações foram as mais 484, depois as segundas 381. De acordo com o número de lactações, as cabras foram agrupadas em classes de um a sete e de um a três para paridade. Comparando cada lactação individual, determinou-se que na primeira lactação as cabras produziram leite significativamente menor do que as cabras nas demais lactações (P<0,05), exceto a sétima. Pesquisas mostraram que o número de lactações tem uma influência significativa na produção de leite (P=0,00). O aumento da fertilidade das cabras afeta significativamente a capacidade de produção de caprinos leiteiros, já que com um número maior de cabritos na ninhada a produção de leite foi significativamente maior (P<0,05). Devido ao maior número de cabritos na ninhada, a produção de leite também aumenta. Da mesma forma, assume-se que o aumento na produção de leite de cabras com dois e três cabritos é uma consequência de uma placenta maior, ou seja, de uma atividade lactogênica mais forte durante a gestação.(AU)

Application of Pulsed Rhythmic Drug Administration to Ovulation Induction Therapy in PCOS Patients with Clomiphene-Resistance: a Retrospective Research.

There is currently a dispute over the choice of ovulation induction treatment for infertile women with polycystic ovary syndrome (PCOS). The objective of this study is to compare the therapeutic effect of pulsed rhythmic administration protocol (PRAP) with conventional letrozole + human menopausal gonadotropin (HMG) in patients with clomiphene-resistance polycystic ovary syndrome (PCOS). A retrospective analysis of 821 intrauterine insemination (IUI) cycles between January 2015 and January 2020 was performed. Of these, 483 cycles were treated with a pulsed rhythmic administration protocol (PRAP), and 338 cycles were treated with conventional letrozole + HMG protocol (LHP). The therapeutic effect of the two protocols has been compared. The pregnancy rate was 18.07% in the LHP and 27.07% in the PRAP. The ongoing pregnancy rate in LHP was 14.46% and in PRAP was 22.73%. The research suggests that PRAP is more effective than LHP and could be an adequate ovulation induction strategy for the IUI cycle of patients with clomiphene-resistance PCOS.

The evolving landscape of donor egg treatment: success, women's choice, and anonymity.

PURPOSE: To analyze donor oocyte (DE) data across 6 years for oocyte usage efficiency, trends, and whether changes impacted outcomes. METHODS: From 2014 to 2019, 323 DE embryo transfers were completed in 200 recipients using oocytes derived of 163 donors. We assessed data for oocytes being freshly retrieved (FRESH-EGG) vs. purchased frozen (FROZEN-EGG); embryos transferred fresh (FRESH-ET) vs. frozen (FROZEN-ET); cycles SHARED (two recipients) vs. SOLE (one recipient); single (SET) vs. double (DET) embryo transfers and usage of PGT-A. Primary outcome was ongoing pregnancy plus live birth (OP/LB) rate. RESULTS: A total of 229 FRESH-EGG (70%) and 94 FROZEN-EGG (30%) cycles were completed. Overall, the use of FRESH-EGG yielded a higher OP/LB compared to FROZEN-EGG (49% vs. 30%, p = 0.001); within the FRESH-EGG group, OP/LB was similar when comparing FRESH-ET vs. FROZEN-ET (58% vs. 45%, p = 0.07). Within the FRESH-ET group, those using FRESH-EGG had a higher OP/LB than those using FROZEN-EGG (58% vs. 27%, p < 0.001). SHARED vs. SOLE cycles (p = 0.6), donor age (21-32 years; p = 0.4), and age of intended parents (maternal p = 0.3, paternal p = 0.2) did not significantly impact OP/LB. Notably, the use of PGT-A did not improve odds for an OP/LB (p = 0.7). CONCLUSION: The use of FRESH-EGG with FRESH-ET without PGT-A remains superior to newer DE treatment combinations. Specifically, the use of FROZEN-EGG and PGT-A did not improve outcomes. Although changing DE practices may enhance experience and affordability, patients and providers must appreciate that choices do not always favorably impact success. Additionally, newly available genetic-ancestry testing may pose longer-term ramifications mandating change in treatment and/or counseling.

Embryo quality, ploidy, and transfer outcomes in male versus female blastocysts.

PURPOSE: The goal is to determine if variations exist between male and female blastocysts in preimplantation measurements of quality and ploidy and in vitro fertilization elective single-embryo transfer (eSET) outcomes. METHODS: A retrospective chart review was conducted from a private fertility center's database of blastocysts undergoing preimplantation genetic testing for aneuploidy, along with details of eSET from this screened cohort. Main outcomes included preimplantation embryo quality and sex-specific eSET outcomes. RESULTS: A total of 3708 embryos from 578 women were evaluated, with 45.9% male and 54.1% female. The majority were High grade. No difference existed between embryo sex and overall morphological grade, inner cell mass or trophectoderm grade, or blastocyst transformation day. Female blastocysts had a higher aneuploidy rate than male blastocysts (P < 0.001). Five hundred thirty-nine eSETs from 392 women were evaluated, with High grade embryos more likely to have implantation (P < 0.001), clinical pregnancy (P < 0.001), and ongoing pregnancy (P = 0.018) than Mid or Low grade embryos. Day 5 blastocysts were more likely to have implantation (P = 0.018), clinical pregnancy (P = 0.005), and ongoing pregnancy (P = 0.018) than day 6 blastocysts. Male and female embryos had similar transfer outcomes, although female day 5 blastocysts were more likely to result in clinical pregnancy (P = 0.012), but not ongoing pregnancy, than female day 6 blastocysts. Male eSET outcomes did not differ by blastocyst transformation day. CONCLUSION: Male and female embryos have comparable grade and quality; however, female embryos were more likely to be aneuploid. Ongoing pregnancy rates did not differ by embryo sex. Day 5 embryos had more favorable transfer outcomes than day 6 embryos.

Effect of polymorphisms of MTHFR in controlled ovarian stimulation: a systematic review and meta-analysis.

OBJECTIVE: Although several studies have reported a potential impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on controlled ovarian stimulation (COS), the results remain controversial. The aim of the systematic review and meta-analysis was to evaluate the effect of MTHFR polymorphism on COS outcomes. METHODS: PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials databases were searched up to December 2, 2020. COS clinical outcomes based on gene polymorphisms were included. Two reviewers independently extracted the data. The primary outcome was the number of oocytes retrieved. The secondary outcomes were the number of metaphase II (MII) oocytes, stimulation duration, basal follicle-stimulating hormone (FSH) level, FSH dosage, positive pregnancy test, ongoing pregnancy rate, clinical pregnancy rate, miscarriage rate, and live birth rate. Meta-analysis was performed using a fixed-effect model or random-effect model with Review Man 5.3.5. Mean difference (MD) with 95% confidence intervals (95%CIs) was calculated for continuous outcomes. The quality assessment of included studies was evaluated by using the Newcastle-Ottawa Scale. RESULTS: Eleven studies were included in the systematic review, and seven studies with 2015 participants were included in the meta-analysis. Basal FSH level was significantly lower in CC homozygotes than TT homozygotes (four studies, 867 participants, MD - 0.54, 95%CI - 0.85 to - 0.23, P = 0.0006; I2 = 0%) of MTHFR (rs1801133). FSH dose was significantly fewer in CC homozygotes compared with CT heterogeneous (three studies, 949 participants, MD - 75.78, 95%CI - 135.23 to - 16.33, P = 0.01; I2 = 32%) or CT/TT model (three studies, 1097 participants, MD - 80.18, 95%CI - 135.54 to - 24.81, P = 0.005; I2 = 42%). Differences in the oocytes retrieved and stimulation duration were insignificant. Gene variants on MTHFR (rs1801133) and MTHFR (rs1801131) were reported in ongoing pregnancy rate, clinical pregnancy rate, and live birth rate. CONCLUSION: Studies to date indicate that polymorphisms of MTHFR could influence basal FSH level and FSH dose. The results could be useful to promote clinical practice on COS protocols. Further studies are needed to evaluate the clinical relevance of the multigene combination on COS.

Elevated Serum Estradiol Levels Do Not Inhibit Implantation During Frozen Embryo Transfer Cycles.

The aim of the study is to determine if the magnitude of serum estradiol levels in blastocyst frozen embryo transfer cycles are associated with clinical pregnancy. A retrospective cohort study of female patients 18-43 years old, who underwent vitrified blastocyst embryo transfers at Tripler Army Medical Center from October 1, 2006, to October 1, 2016, was evaluated to determine the impact of estradiol levels on ongoing pregnancy rates in frozen embryo transfer cycles. The study included 173 total frozen embryo transfer cycles during the 10-year study period. The mean age at time of transfer was 34.5 years old (±4.4) with a majority of women undergoing double embryo transfer (70%). There was no statistical difference in ongoing pregnancy rates across estradiol levels (p = 0.80). However, at estradiol levels >3000 pg/mL, a statistically significant ongoing pregnancy rate was observed (p = 0.009). Ongoing pregnancy rate in frozen embryo transfer cycles is not negatively impacted by elevated estradiol levels.

Biosimilar recombinant follitropin alfa preparations versus the reference product (Gonal-F®) in couples undergoing assisted reproductive technology treatment: a systematic review and meta-analysis.

BACKGROUND: Live birth has increasingly been identified as the standard clinical approach to measure the success of medically assisted reproduction (MAR). However, previous analyses comparing biosimilar preparations of follitropin alfa versus the reference product (GONAL-f®, Merck KGaA, Darmstadt, Germany or GONAL-f® RFF; EMD Serono, Inc., Rockland, MA), have had insufficient power to detect differences in clinically meaningful outcomes such as live birth. METHODS: Medline, Embase, the Cochrane Library, Web of Science and clinical trial registries were searched for randomised controlled trials (RCTs) and conference abstracts comparing biosimilar follitropin alfa versus the reference product in controlled ovarian stimulation (COS) cycles published before 31 October 2020. Only studies in humans and publications in English were included. Retrieved studies were screened independently by two authors based on titles and abstracts, and then by full text. INCLUSION CRITERIA: RCTs comparing follitropin alfa biosimilar preparations with the reference product in infertile patients of any age, with any type of infertility for any duration, undergoing COS for the purposes of MAR treatment (including frozen cycles). The primary outcome was live birth. Combined data for biosimilar preparations were analysed using a fixed-effects model. RESULTS: From 292 unique records identified, 17 studies were included in the systematic review, representing five unique RCTs that were included in the meta-analysis. Rates of live birth (RR = 0.83, 95% CI 0.71, 0.97; 4 RCTs, n = 1881, I2 = 0%), clinical pregnancy (RR = 0.82, 95% CI 0.72, 0.94; 4 RCTs, n = 2222, I2 = 0%) and ongoing pregnancy (RR = 0.81, 95% CI 0.68, 0.96; 4 RCTs, n = 1232, I2 = 0%) were significantly lower with biosimilar preparations versus the reference product. Rates of cumulative live birth and cumulative clinical pregnancy were also significantly lower with biosimilars versus the reference product. There was high risk of publication bias. CONCLUSIONS: This meta-analysis included data from RCTs evaluating the efficacy and safety of the biosimilar follitropin alfa preparations and demonstrated lower probability of live birth and pregnancy (ongoing and clinical) in couples treated with biosimilar preparations compared with the reference product. This study provides more insight into the differences between biosimilar r-hFSH preparations and the reference product than previously reported. TRIAL REGISTRATION: Registration number: CRD42019121992 .

Changes in thyroid function during controlled ovarian hyperstimulation (COH) and its impact on assisted reproduction technology (ART) outcomes: a systematic review and meta-analysis.

BACKGROUND: To investigate the thyroid function changes during controlled ovarian hyperstimulation (COH) and ascertain its impact on reproductive outcomes. METHODS: We conducted meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed to identify studies reported changes in thyroid parameters during COH. We analyzed thyroid-stimulating hormone (TSH) levels, free thyroxin (fT4) levels, changes in estrogens (E2), thyroxine-binding globulin (TBG), relative risks (RRs) of clinical pregnancy rate (CPR), live birth rate (LBR), and mean difference (MD) of TSH increment between the miscarriage group and ongoing pregnancy group. RESULTS: This meta-analysis included fifteen individual studies (n = 1665 subjects). At the end of COH, the mean TSH (2.53 mIU/L; 95% CI, 2.19 to 2.88; I2 = 92.9%) exceeded the upper limit (2.5 mIU/L) and remained above the threshold until one month following embryo transfer (ET). Thyroxin decreased from baseline to the end of COH (-0.18 ng/l; 95% CI, -0.35 to 0.00; I2 = 92.2%). The CPR and LBR of patients with TSH exceeding the cutoff after COH were significantly lower than those of patients with TSH below the threshold (CPR: RR, 0.62; 95% CI, 0.47 to 0.82; I2 = 0.0% and LBR: RR, 0.64; 95% CI, 0.44 to 0.92; I2 = 0.0%). The MD of the increment in TSH levels between the miscarriage and ongoing pregnancy groups was 0.40 mIU/L (95% CI, 0.15 to 0.65; I2 = 0.0%). CONCLUSIONS: This meta-analysis shows that TSH increases and fT4 decreases during COH. COH-induced thyroid disorder impairs reproductive outcomes.

International Committee for Monitoring Assisted Reproductive Technologies (ICMART): world report on assisted reproductive technologies, 2013.

OBJECTIVE: To report the utilization, effectiveness, and safety of practices in assisted reproductive technology (ART) globally in 2013 and assess global trends over time. DESIGN: Retrospective, cross-sectional survey on the utilization, effectiveness, and safety of ART procedures performed globally during 2013. SETTING: Seventy-five countries and 2,639 ART clinics. PATIENT(S): Women and men undergoing ART procedures. INTERVENTION(S): All ART. MAIN OUTCOME MEASURE(S): The ART cycles and outcomes on country-by-country, regional, and global levels. Aggregate country data were processed and analyzed based on methods developed by the International Committee for Monitoring Assisted Reproductive Technology (ICMART). RESULT(S): A total of 1,858,500 ART cycles were conducted for the treatment year 2013 across 2,639 clinics in 75 participating countries with a global participation rate of 73.6%. Reported and estimated data suggest 1,160,474 embryo transfers (ETs) were performed resulting in >344,317 babies. From 2012 to 2013, the number of reported aspiration and frozen ET cycles increased by 3% and 16.4%, respectively. The proportion of women aged >40 years undergoing nondonor ART increased from 25.2% in 2012 to 26.3% in 2013. As a percentage of nondonor aspiration cycles, intracytoplasmic sperm injection (ICSI) was similar to results for 2012. The in vitro fertilization (IVF)/ICSI combined delivery rates per fresh aspiration and frozen ET cycles were 24.2% and 22.8%, respectively. In fresh nondonor cycles, single ET increased from 33.7% in 2012 to 36.5% in 2013, whereas the average number of transferred embryos was 1.81-again with wide country variation. The rate of twin deliveries after fresh nondonor transfers was 17.9%; the triplet rate was 0.7%. In frozen ET cycles performed in 2013, single ET was used in 57.6%, with an average of 1.49 embryos transferred and twin and triplet rates of 10.8% and 0.4%, respectively. The cumulative delivery rate per aspiration was 30.4%, similar to that in 2012. Perinatal mortality rate per 1,000 births was 22.2% after fresh IVF/ICSI and 16.8% after frozen ET. The data presented depended on the quality and completeness of the data submitted by individual countries. This report covers approximately two-thirds of world ART activity. Continued efforts to improve the quality and consistency of reporting ART data by registries are still needed. CONCLUSION(S): Reported ART cycles, effectiveness, and safety increased between 2012 and 2013 with adoption of a better method for estimating unreported cycles.

Perinatal outcomes in singleton pregnancies after in vitro fertilization cycles over 24 years.

OBJECTIVE: To determine how a shift in clinical practice along with laboratory changes has impacted singleton perinatal outcomes after autologous in vitro fertilization (IVF) cycles. DESIGN: Retrospective cohort. SETTING: Single academic fertility clinic. PATIENT(S): Singleton live births resulting from all IVF cycles (n = 14,424) from August 1, 1995 to October 31, 2019. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth weight, large for gestational age (GA), small for GA, and preterm birth. RESULT(S): The entire cohort consisted of 9,280 fresh and 5,144 frozen IVF cycles. Maternal age, parity, body mass index, neonatal sex, and GA at delivery were similar in both groups. There was a decrease in adjusted birth weight per year over the study period for the entire cohort of IVF cycles (-4.42g, 95% confidence interval [CI]: -6.63g to -2.22g). Rates of large for GA newborns decreased by 1.7% (95% CI: 2.9% to 0.6%) annually across the entire cohort of IVF cycles. Furthermore, there was a decrease in annual rates of preterm birth before 32 weeks by 3.2% (95% CI: 5.9% to 0.5%) across the entire cohort of IVF cycles. Trends were also seen in annual reduction of rates of preterm birth before 37 and 28 weeks. CONCLUSION(S): With the gradual evolution of clinical and IVF laboratory practices, there has been a decrease in birth weight over 24 years for the entire cohort of IVF cycles. Concurrently, noteworthy practice changes have resulted in an improvement in IVF outcomes with decreased rates of large for GA newborns and preterm birth before 32 weeks for the entire cohort of IVF cycles.