Placental pathology in live births conceived with in vitro fertilization after fresh and frozen embryo transfer.

BACKGROUND: The availability and use of frozen embryos after ovarian hyperstimulation for assisted reproduction has increased with improvement in vitrification techniques and the rise of preimplantation genetic testing. However, there are conflicting data regarding whether obstetric outcomes differ between fresh and frozen embryo transfer cycles. OBJECTIVE: To compare placental pathology from live births arising from fresh and frozen embryo transfer cycles. MATERIALS AND METHODS: A cohort of 1140 live births with placental pathology arising from autologous in vitro fertilization cycles with fresh or frozen programmed transfer performed at MGH Fertility Center between 2004 and 2017 was retrospectively reviewed. An experienced placental pathologist categorized the reported placental pathology as anatomic, infectious, inflammatory, or vascular/thrombotic. Our primary outcomes were differences in these placental pathologies between the 2 groups. Patient demographic, cycle, and birth outcomes were compared with the use of χ2 tests, Student t test, or nonparametric tests, as appropriate. Multivariate logistic regression models were used to compare placental pathology between the fresh and frozen transfer groups. RESULTS: Of the 1140 cycles included in our analysis, 929 arose from fresh embryo transfers (81.3%) and 211 arose from programmed frozen embryo transfers (18.5%). For both transfer types, the average age of the women at time of treatment was 35 years; mean body mass indices were within the normal range (23.6 kg/m2 for fresh transfers and 23.2 kg/m2 for frozen transfers, P = .26), and mean day 3 follicle-stimulating hormone values were 7.1 and 7.0 IU/L (P = .44), respectively. Deliveries occurred on average at 37.5 and 38.0 weeks' gestational age (P = .04) in the fresh versus frozen transfer group, with similar rates of obstetric complications. However, frozen transfers were more likely to be associated with marginal cord insertion (adjusted odds ratio, 1.87; confidence interval, 1.21, 2.91; P = .01), accessory lobe formation (adjusted odds ratio, 2.96; confidence interval, 1.12, 7.79; P = 0.03), subchorionic thrombi (adjusted odds ratio, 3.72; confidence interval, 1.80, 7.71; P < .001), and fetal vascular malperfusion characteristics with cord anomalies (adjusted odds ratio, 2.34; confidence interval, 1.22, 4.46; P = .01). These trends persisted when we analyzed day 5 transfers alone, and single frozen embryo transfers remained associated with increased rates of subchorionic thrombi compared to single fresh embryo transfers. CONCLUSION: Pregnancies arising from frozen embryo transfers demonstrated more anatomic and vascular placental pathology than those from fresh transfers in our cohort of patients, despite similar maternal outcomes. More research is needed to explore how these differences in pathology may influence obstetric and perinatal outcomes.

Impact of obesity on male and female reproductive outcomes.

PURPOSE OF REVIEW: The association between obesity and infertility has gained increasing provider and public awareness. The purpose of this review is to outline the recent research into the pathophysiology regarding obesity and its impact of reproductive function in both women and men. RECENT FINDINGS: A BMI more than 25 has a detrimental impact on the hypothalamus-pituitary-gonadal (HPG) axis in both men and women, leading to alterations of HPG hormones, gametogenesis, as well as an increase in inflammation and lipotoxicity from excessive adipose tissue. Additionally, BMI likely impacts assisted reproductive technology (ART) outcomes, with a greater influence on women than men. Studies regarding weight loss interventions are heterogenous in methods and outcomes, and it is difficult to extrapolate from current data if weight loss truly leads to improved outcomes. SUMMARY: Elevated BMI induces changes in the HPG axis, hormone levels, gametogenesis, and adverse ART outcomes. Inconsistencies regarding weight loss interventions make it difficult to assess the impact on outcomes after weight loss interventions.

Placental pathology of term singleton live births conceived with fresh embryo transfer compared with those conceived without assisted reproductive technology.

OBJECTIVE: To compare placental pathology from term singleton live births conceived with fresh embryo transfer vs. those conceived without assisted reproductive technology (ART). DESIGN: Retrospective cohort study. SETTING: Academic fertility center. PATIENT(S): Women with a term singleton live birth who conceived after fresh autologous in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles (ART group) and those who conceived without ART. INTERVENTION(S): An experienced placental pathologist categorized placental pathology as anatomic, inflammatory, or vascular. Patient characteristics were compared by chi-squared tests, Student's t-test, or nonparametric tests. Multivariate logistic regression models were used to compare placental pathology between pregnancies conceived with and without ART. MAIN OUTCOME MEASURE(S): Incidence of anatomic, inflammatory, and vascular placental pathology. RESULT(S): There was a higher incidence of placental pathology in the ART group (n = 511) than in the non-ART group (n = 121), specifically anatomic (adjusted odds ratio [aOR] 2.50, 95% confidence interval [CI] 1.42-4.40) and vascular (aOR 2.00, 95% CI 1.13-3.53) pathology. These findings were driven primarily by the significantly higher odds of anatomic (aOR 2.97, 95% CI 1.55-5.66) and vascular (aOR 1.98, 95% CI 1.04-3.75) pathology observed in ICSI pregnancies. Single blastocyst transfers remained associated with increased anatomic pathology (ART: aOR 4.89, 95% CI 2.28-10.49; ICSI: aOR 3.38, 95% CI 1.49-7.71). CONCLUSION(S): Fresh embryo transfer is associated with increased anatomic and vascular placental pathology in term singleton live births compared with conception without ART. This finding should be investigated prospectively in a larger cohort of patients.

Virtual Compared With In-Clinic Transvaginal Ultrasonography for Ovarian Reserve Assessment.

OBJECTIVE: To evaluate noninferiority of virtual transvaginal ultrasonography compared with in-clinic ultrasonography for ovarian reserve assessment. METHODS: We conducted a single-site, head-to-head crossover trial. Participants performed self-administered virtual transvaginal ultrasonography at home, guided by a remote-certified ultrasound technologist, then underwent transvaginal ultrasonography in-clinic with another ultrasound technologist. Participants were women in the greater Boston area interested in evaluating ovarian reserve and recruited through social media, health care referrals, and professional networks. The uterus and ovaries were captured in sagittal and transverse views. These randomized recordings were reviewed by two or three independent, blinded reproductive endocrinologists. The primary outcome was noninferiority of the rate of clinical quality imaging produced at home compared with in clinic. Sample size was selected for greater than 90% power, given the 18% noninferiority margin. Secondary outcomes included antral follicle count equivalency and net promoter score superiority. RESULTS: Fifty-six women were enrolled from December 2020 to May 2021. Participants varied in age (19-35 years), BMI (19.5-33.9), and occupation. Ninety-six percent of virtual and 98% of in-clinic images met "clinical quality." The difference of -2.4% (97.5% CI lower bound -5.5%) was within the noninferiority margin (18%). Antral follicle counts were equivalent across settings, with a difference in follicles (0.23, 95% CI -0.36 to 0.82) within the equivalence margin (2.65). Virtual examinations had superior net promoter scores (58.1 points, 97.5% CI of difference 37.3-79.0, P<.01), indicating greater satisfaction with the virtual experience. CONCLUSION: Virtual transvaginal ultrasonography remotely guided by an ultrasonography technologist is noninferior to in-clinic transvaginal ultrasonography for producing clinical quality images and is equivalent for estimating antral follicle count. Virtual transvaginal ultrasonography had superior patient satisfaction and has potential to significantly expand patient access to fertility care. FUNDING SOURCE: This study was sponsored by Turtle Health. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04687189.

Vanishing Twins Conceived Through Fresh In Vitro Fertilization: Obstetric Outcomes and Placental Pathology.

OBJECTIVE: To characterize the obstetric outcomes and placental pathology in live births arising from vanishing twin pregnancies compared with nonreduced in vitro fertilization (IVF) pregnancies. METHODS: This is a retrospective cohort study of live births resulting from fresh embryo transfers after IVF cycles with autologous oocytes from 2004 through 2017 at a large academic fertility center. Clinical information and pathology reports were reviewed. Placental diagnoses were coded using established nosology by expert placental pathologists. Analysis of variance, Kruskal-Wallis, Pearson's χ, and Fisher exact tests were used, as appropriate, to compare pathology categories between pregnancy outcomes. Mixed effects logistic regression models were generated to reveal the association between pregnancy outcome and placenta pathology, controlling for pregnancies arising in the same woman and various suspected confounders. RESULTS: Of 905 fresh autologous IVF cycles with placental pathology available for review, we identified 73 vanishing twin pregnancies (8.1%), 556 singleton pregnancies (61.4%), and 276 twin pregnancies (30.5%). Vanishing twin syndrome was not associated with preterm delivery, route of delivery, growth restriction or other obstetric outcomes as compared with IVF singleton pregnancies. However, vanishing twin syndrome pregnancies showed distinctive placental pathologies including an increased rate of small placentas (less than the 10th percentile by weight), with more anatomical abnormalities than IVF singleton pregnancies (odds ratio 1.73, 95% CI 0.94-3.19; adjusted odds ratio 2.15, 95% CI 1.08-4.28). The frequency of placental vascular and inflammatory pathologies associated with IVF vanishing twin syndrome pregnancies were similar to that of IVF singleton pregnancies. Loss of a twin after 8 weeks of gestation was not associated with greater risks of placental pathologies. CONCLUSION: In vitro fertilization pregnancies affected by vanishing twin syndrome did not have significant differences in obstetric or perinatal outcomes as compared with twin or singleton gestations. However, early twin loss was potentially associated with differences in placental development associated with a higher rate of small placentas and other anatomic pathologies.

Are the amounts of vitamins in commercially available dietary supplement formulations relevant for the management of psychiatric disorders in children?

AIM: To investigate whether micronutrient supplements shown through research to have perceived benefits in the treatment of psychological/psychiatric symptoms in children have similar vitamin ingredients and doses to over-the-counter dietary supplements. METHODS: We conducted a systematic review to identify studies that used micronutrients for the treatment of psychological/psychiatric symptoms in children with documented benefits; 13 different supplements were identified that included vitamin ingredients. They were compared with the vitamin composition of 22 over-the-counter child-targeted supplements available in New Zealand. RESULTS: The vitamin ingredients were comparable across the research and commercially available supplements. However, the median vitamin daily doses in research supplements were found to be greater than those of over-the-counter supplements, with most mean differences being significant, including vitamins B1, B3, B6, B7, B12, C and D (p<0.05), B5 and B9 (p<0.001), but not vitamins A or B2. CONCLUSIONS: Micronutrient supplements found to show potential benefit in research with a focus on improving psychological/psychiatric symptoms in children have a significantly greater vitamin dose than over-the-counter supplements. Therefore, the results found in micronutrient research studies cannot be extrapolated to over-the-counter supplements. Comparing the myriad ingredients and dosages in micronutrient supplements is, however, a complex process and further investigation is required to understand fully the importance of our findings.

Darwin's legacy: an evolutionary view of women's reproductive and sexual functioning.

On the Origin of species, published just over 150 years ago, has deeply influenced thinking in both scientific and wider communities. Darwin's legacy includes recognition of the fact that all organisms evolve; that variation within and between species is natural and normal; and that an evolutionary approach to understanding the sources and consequences of this variation comprises theoretical frameworks, testable hypotheses, and rigorously collected evidence. With an eye toward facilitating communication and productive collaboration among researchers from different intellectual traditions who nonetheless share a common interest in women's reproductive and sexual functioning, we discuss evolutionary concepts and models, summarize the known variability in ovarian functioning and consider the implications of this variability for conducting sex research, and evaluate the relative merits of various biomarkers that serve as proxy measurements of a woman's reproductive and hormonal status. With these perspectives and methods from reproductive ecology at hand, we examine several contentious issues: the links between hormones and sexuality in premenopausal and perimenopausal women, the causes of premenstrual syndrome, and the existence (or not) of menstrual synchrony. In none of these cases is as much known as is often claimed. In each, there are abundant opportunities for innovative, albeit challenging, research.