Impact of the COVID-19 Pandemic on Access to Fertility Care: A Retrospective Study at a University-Affiliated Fertility Practice.

OBJECTIVE: To elucidate the impact of the COVID-19 pandemic on access to fertility services. METHODS: A retrospective quality improvement study was conducted at a university-affiliated fertility practice in southwestern Ontario. Annual procedural volumes for intrauterine and donor inseminations (IUI/DI), in vitro fertilization and intracytoplasmic sperm injections (IVF/ICSI), and frozen embryo transfers (FET) during the COVID-19-affected year were compared with mean annual volumes from the 2 preceding years. In addition, volumes for the same procedures were compared between the first quarter of 2021 and mean first quarter volumes from 2018 to 2019. Piecewise linear regressions were conducted to evaluate whether any changes in monthly procedural volume were attributable to the COVID-19 pandemic. RESULTS: In 2020, our fertility practice attained the mean annual volumes of 89.7% for IUI/DI, 69.0% for IVF/ICSI, and 60.6% for FET. In contrast, in 2021, we performed mean first quarter volumes of 130.1% for IUI/DI, 164.3% for IVF/ICSI, and 126.8% for FET. The slopes of the pre- and post-COVID-19 segments of the piecewise linear regressions were significantly different for IUI/DI (P < 0.001) and IVF/ICSI (P = 0.001), but not for FET (P = 0.133). CONCLUSION: The COVID-19 pandemic resulted in decreased annual volumes of medically assisted reproductive procedures at a university-affiliated fertility practice in southwestern Ontario. Impact on monthly procedural volume was confirmed for IUI/DI and IVF/ICSI by linear regression. Local adaptations helped compensate and exceed expected volumes in 2021. As a result, the COVID-19 pandemic resulted in a short-lived limitation in access to fertility care.

Sub-endometrial contractility or computer-enhanced 3-D modeling scoring of the endometrium before embryo transfer: are they better than measuring endometrial thickness?

PURPOSE: Recent studies have focused on transvaginal ultrasound measurement (TVUS) of sub-endometrial contractility and computer-enhanced 3-D modeling scoring of the endometrium prior to embryo transfer (ET).The aim of this study was to compare pregnancy outcome of patients who performed the 3-D scoring or the sub-endometrial measurement prior to the ET with patients that did not perform those procedures. METHODS: A single center retrospective cohort study of 635 freeze/thaw cycles of blastocysts vitrified on day 5 and transferred between January 2016 and August 2016. RESULTS: We compared the patients who performed 3-D scoring with the control group and found comparable patients' characteristics, clinical pregnancy rates (42% vs. 44.3, p = NS, respectively), and ongoing pregnancy rates (31.7% vs. 33.9%, p = NS).We then compared the patients who performed the sub-endometrial wave measurements with the control group and found similar findings. The clinical pregnancy rate (38.2% vs. 44.3, p = NS, respectively) and the ongoing pregnancy rate (30.8% vs. 33.9%) were comparable between the two groups. We performed a regression analysis to examine the independent contribution of different variables to the ongoing pregnancy rates. Both the 3-D and the wave count procedures were not found to have any influence on the ongoing pregnancy rates. CONCLUSIONS: Although new ultrasonic methods of evaluating the endometrium have been proposed during the last years, these methods have not been shown to improve the pregnancy rates compared to the original method of assessing the endometrium by measuring the endometrial thickness.

Time-to-pregnancy and offspring finger-length ratio (2D:4D).

OBJECTIVES: Time-to-Pregnancy (TTP) is an epidemiological tool to assess couple fecundity. The finger digit ratio (2D:4D) has been suggested as a marker of androgen exposure in utero. Maternal, paternal, or couple-mediated factors related to fecundity may also have an effect on androgen exposure during pregnancy. We aimed to investigate the association between TTP, infertility, or use of Assisted Reproductive Technologies (ART) and offspring 2D:4D. METHODS: Data from 673 mother-child pairs were collected from questionnaires in the Maternal-Infant Research on Environmental Chemicals (MIREC) study across 10 cities in Canada. The mean maternal age was 33.4 years (SD 4.7), with a median gestational age of 12.1 weeks (SD 1.3), at the time of recruitment. Our study included 338 girls and 335 boys, and the mean age of the children at follow-up was 3.5 years (SD 1.0). TTP was assessed through questionnaires during the first trimester of pregnancy. Digital photographs of both hands were taken in a follow-up study to calculate the children's 2D:4D (2-5 years). anova, t tests, and multiple linear regression analyses were conducted. RESULTS: Boys had significantly lower mean 2D:4Ds (0.936 ±0.041 in right hand, 0.936 ±0.040 in left hand) compared to girls (0.948 ±0.038 in right hand, 0.945 ±0.038 in left hand). The mean 2D:4D did not differ according to TTP, infertility, or use of ART. The only factors associated with the child's 2D:4D were the child's age and maternal 2D:4D. CONCLUSIONS: Our study does not support an association between TTP, infertility, or use of ART and children's 2D:4D.

Folate status of women in Toronto: Implications of folate fortification and supplementation.

OBJECTIVES: To assess the percentage of women of childbearing age with suboptimal levels of folate for protecting against neural tube defects (<906 nM), and assess folate status among the elderly. METHODS: A total of 1,035 anonymous blood samples from a centralized clinical laboratory, with a catchment area across the Greater Toronto Area, were assessed for red blood cell (RBC) folate concentrations using a chemiluminescent immunoassay. Folate analysis was requested by physicians as part of clinical care. Available data included age, sex, and RBC folate concentration. Descriptive statistics were used to characterize the percent of women who had suboptimal blood folate concentrations, and a multiple regression was used to analyze determinants of folate status. RESULTS: Our data from 2013 show that 7% of women of childbearing age (15-45 years) had RBC folate concentrations below 906 nM, a substantially lower percentage than in our 2006 study (40%). Results from the multiple regression showed that age is a significant positive predictor of higher RBC folate status (p < 0.001). CONCLUSION: Compared to our earlier data, we report a significant decrease in the suboptimal folate status among women of childbearing age. We also show that age is a predictor of higher RBC folate levels. Our data are limited due to a lack of information regarding patient or physician characteristics, and to the nature of our sample, yet our results are consistent with the continued increase in folate status observed among several population-level studies in the US and Canada post-fortification. Further research is needed to determine the reasons for and future implications of this continued increase in the elderly.

The Effectiveness of Folate-Fortified Oral Contraceptives in Maintaining Optimal Folate Levels to Protect Against Neural Tube Defects: A Systematic Review.

OBJECTIVE: To conduct a systematic review evaluating the effectiveness of a folate-fortified oral contraceptive preparation in increasing blood folate concentrations to levels providing optimal protection against neural tube defects (> 906 nmol/L). METHODS: We searched Medline, EMBASE, Web of Science, and the Cochrane Library for human studies published from inception to June 2013 that evaluated oral contraceptive use and folate status. Case-control studies, cohort studies, and clinical trials were included. Efficacy and bioequivalence data were evaluated from included studies. RESULTS: Overall, efficacy and bioequivalence data for the folate-fortified oral contraceptive show that it is at least as effective as folic acid alone in raising blood folate concentrations, and that the concomitant administration of folate with the oral contraceptive component does not affect its absorption or kinetics. CONCLUSION: A folate-fortified oral contraceptive preparation provides an option for women to maintain blood folate levels, especially those who may be planning a family after the cessation of oral contraceptive therapy.

Objectif : Mener une analyse systématique de l'efficacité d'un contraceptif oral enrichi en folate pour ce qui est d'accroître les concentrations sanguines en folate jusqu'aux niveaux offrant une protection optimale contre les anomalies du tube neural (> 906 nmol/l). Méthodes : Nous avons mené des recherches dans Medline, EMBASE, Web of Science, et la Cochrane library en vue d'en tirer les études menées chez l'homme, publiées entre le début de nos travaux et juin 2013, qui ont évalué l'utilisation de contraceptifs oraux et les taux de folate. Les études cas-témoins, les études de cohorte et les essais cliniques ont été admis aux fins de notre analyse. Les issues ont été soumises à une méta-analyse faisant appel à un modèle à effets aléatoires. Résultats : De façon globale, les données sur l'efficacité et la bioéquivalence en ce qui concerne les contraceptifs oraux enrichis en folate indiquent que ceux-ci sont au moins aussi efficaces que l'acide folique administré seul pour ce qui est d'augmenter les concentrations sanguines en folate; elles indiquent également que l'administration concomitante de folate et d'un composé contraceptif oral n'en affecte ni l'absorption ni la cinétique. Conclusion : Les contraceptifs oraux enrichis en folate offrent une option aux femmes pour le maintien de leurs taux sanguins de folate; cette option s'avère particulièrement adaptée aux femmes qui pourraient souhaiter devenir enceintes à la suite de l'abandon de la contraception orale.

Association Between Use of Oral Contraceptives and Folate Status: A Systematic Review and Meta-Analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of the effect of oral contraceptive use on plasma and red blood cell (RBC) folate concentrations. METHODS: We searched Medline, EMBASE, Web of Science, and the Cochrane library for human studies published from inception to June 2013 evaluating oral contraceptive use and folate status. Case-control studies, cohort studies, and clinical trials were included. A random-effects model of outcomes was used for the meta-analysis. RESULTS: A total of 2831 women in 17 studies were included in the analysis. In those whose plasma folate concentrations were available, there was a significant folate-lowering effect of oral contraceptives observed (mean reduction 1.27 µg/L; 95% CI 1.85 to 0.69, P < 0.001). Similarly, after analyzing data from 1389 women in 12 studies whose RBC folate concentrations were available, significantly lower folate status was observed among oral contraceptive users (mean reduction 59.32 µg/L; 95% CI 58.03 to 23.04, P < 0.001). CONCLUSION: Because of the reduction in blood folate concentrations associated with the use of oral contraceptives, it is critical for women of childbearing age to continue folate supplementation during oral contraceptive use.

Objectif : Mener une analyse systématique et une méta-analyse quant à l'effet du recours à la contraception orale sur les concentrations plasmatiques et érythrocytaires en folate. Méthodes : Nous avons mené des recherches dans Medline, EMBASE, Web of Science et la Cochrane library en vue d'en tirer les études menées chez l'homme, publiées entre le début de nos travaux et juin 2013, qui ont évalué l'utilisation de contraceptifs oraux et les taux de folate. Les études cas-témoins, les études de cohorte et les essais cliniques ont été admis aux fins de notre analyse. Un modèle à effets aléatoires quant aux issues a été utilisé dans le cadre de la méta-analyse. Résultats : Au total, 2 831 femmes issues de 17 études ont été admises à l'analyse. Chez les femmes pour lesquelles les concentrations plasmatiques en folate étaient disponibles, nous avons constaté que les contraceptifs oraux exerçaient un effet considérable d'atténuation de ces concentrations (baisse moyenne, 1,27 µg/l; IC à 95 %, 1,85 - 0,69, P < 0,001). De façon semblable, après avoir analysé les données traitant de 1 389 femmes issues de 12 études pour lesquelles les concentrations érythrocytaires en folate étaient disponibles, nous avons constaté une baisse considérable de ces concentrations chez les utilisatrices de contraceptifs oraux (baisse moyenne, 59,32 µg/l; IC à 95 %, 58,03 - 23,04, P < 0,001). Conclusion : En raison de la baisse des concentrations sanguines en folate qui sont associées à l'utilisation de contraceptifs oraux, il est crucial que les femmes en âge de procréer qui ont recours à une telle contraception continuent à prendre une supplémentation en folate.

Pregnancy-induced changes in the long-term pharmacokinetics of 1.1 mg vs. 5 mg folic acid: a randomized clinical trial.

The objective of this randomized clinical trial was to compare steady-state gestational RBC and plasma folate concentrations in pregnant women supplementing daily with 1.1 mg (regular dose) vs. 5 mg (high dose) folic acid. Thirty-seven pregnant women, who were not previously taking folic acid, were enrolled in this open-label, 2-arm, randomized clinical trial after informed consent. Participants were randomly assigned either 1.1 or 5 mg of folic acid-containing prenatals until gestational age (g.a.) 30 weeks. Plasma and RBC folate concentrations were measured at baseline, g.a.6 weeks, g.a.12 weeks, and g.a.30 weeks using a chemiluminescent immunoassay. Results showed sustained significant increase in RBC folate in the 5 mg group between g.a.6 weeks and g.a.30 weeks (P < 0.001), and between g.a.12 weeks and g.a.30 weeks (P < 0.01), whereas a significant increase in RBC folate concentrations was observed in the 1.1 mg group only between g.a.12 weeks to g.a.30 weeks (P < 0.05). Plasma folate increased in both groups from baseline to g.a.6 weeks, and then decreased between g.a.6 weeks and g.a.30 weeks, but this was not statistically significant. Plasma concentrations at g.a.30 weeks in both groups were comparable to their respective baseline concentrations. Thus, physiological changes in pregnancy alter long-term folate pharmacokinetics. Despite supplementation over an extended period of time, steady-state does not seem to be achieved in either dose group within our study.

The role of social media in recruiting for clinical trials in pregnancy.

BACKGROUND: Recruitment of women in the periconceptional period to clinical studies using traditional advertising through medical establishments is difficult and slow. Given the widespread use of the internet as a source for medical information and research, we analyze the impact of social media in the second phase of an ongoing randomized, open-label clinical trial among pregnant women. This study aims to assess the effectiveness of social media as a recruitment tool through the comparison of diverse recruitment techniques in two different phases of the trial. METHODS: Recruitment in Phase 1 of the study consisted solely of traditional healthcare-based sources. This was compared to Phase 2 of the study where traditional recruitment was continued and expanded, while social media was used as a supplementary source. Yearly recruitment and recruitment rates in the two phases were compared using the Mann Whitney U test. The contributions of each recruitment source to overall recruitment were analyzed, and the impact of potential confounders on recruitment rate was evaluated using a multiple regression and Interrupted Time Series Analysis. RESULTS: In the first phase of the study, with over 56 months of recruitment using traditional sources, 35 women were enrolled in the study, resulting in a mean rate of ±0.62 recruits/month. In the 6 months implementing recruitment through social media, 45 women were recruited, for a 12-fold higher rate of ±7.5 recruits/month. Attrition rates remained constant, suggesting that social media had a positive impact on recruitment. The Interrupted Time Series Analysis detected a significant difference in recruitment after the intervention of social media (p<0.0001) with an evident increase in the number of recruits observed after the use of social media. CONCLUSIONS: Clinicians and scientists recruiting for clinical studies should learn how to use online social media platforms to improve recruitment rates, thus increasing recruitment efficiency and cost-effectiveness.