When the Ideal Meets the Feasible: Constructing a Protocol for Developmental Assessment at Early School-Age

Objective: To describe development of a methodology for an outcome study of children born following in-vitro fertilization or spontaneously-conceived, as a model for defining normal and below-normal development of school-age children for research purposes.Study Design: The main issues addressed were defining the major health and developmental domains to be investigated, selection of age-appropriate validated instruments, considering time constraints to maximize compliance, and budgetary limitations. The final protocol included a half-hour structured telephone interview with mothers of all 759 children and a 2-h developmental assessment of 294 of them. Each of the instruments and recruiting methods are described in terms of the abovementioned considerations.Results: Almost all of the mothers who agreed to be interviewed completed it within the half-hour allotted; however only about half of those who agreed to bring the child for the developmental assessment actually did so. The entire examination battery, assessing cognitive ability, executive functions, attention, and learning skills, was completed by almost all 294 children. There was a significant degree of agreement between the maternal report of the child's reading, writing and arithmetic skills and the in-person examination, as well as regarding the child's weight and height measurements.Conclusion: The findings lend support for a low-budget study, relying on telephone interviews. However, limitations such as the validity of maternal report and recall bias must be taken into consideration

The effects of maternal thyroid hormone function on early pregnancy

PURPOSE OF REVIEW: It is unclear whether pregnancy outcomes are impacted by nonovert thyroid disease, and whether detection and treatment of abnormalities improve outcomes. Consequently, there is an ongoing debate regarding universal thyroid screening in pregnancy. A lack of solid evidence has prompted researchers to evaluate the role of screening and to examine pregnancy outcomes in women with thyroid dysfunction. In addition, as IVF has developed into a commonly used procedure, its impact on thyroid function has also been investigated. The most current literature on these topics will be summarized in this review. RECENT FINDINGS: The multiple societies that have published guidelines on thyroid disease in pregnancy have developed different recommendations, with none definitively advocating for universal screening at this time. However, recent studies examining the role of screening have supported it from an economic and prevalence standpoint. Despite this, evidence has failed to consistently demonstrate that treatment of nonovert thyroid disorders improves maternal and fetal outcomes. Recent research does suggest that close monitoring for and treatment of thyroid dysfunction is warranted in women undergoing IVF. SUMMARY: Further research must be performed to determine whether treatment of nonovert thyroid disease during pregnancy impacts outcomes. Concrete evidence will likely influence the universal screening debate

In Vitro Fertilization Pregnancy Rates in Levothyroxine-Treated Women With Hypothyroidism Compared to Women Without Thyroid Dysfunction Disorders

Background: Untreated hypothyroidism can lead to ovulatory dysfunction resulting in oligo-amenorrhea. Treatment with levothyroxine can reverse such dysfunction and thus should improve fertility. The purpose of this retrospective study was to assess whether in vitro fertilization (IVF) pregnancy rates differ in levothyroxinetreated women with hypothyroidism compared to women without thyroid dysfunction/disorders. Methods: Treated hypothyroid and euthyroid women undergoing IVF at an academic IVF center were studied after Institutional Review Board approval. Women with hypothyroidism were treated with levothyroxine 0.025– 0.15 mg/day for at least 3 months to maintain baseline thyrotropin (TSH) levels of 0.35–4.0 lU/mL prior to commencing IVF treatment (HYPO-Rx group). Causes of infertility were similar in both groups with the exception of male factor, which was more common in the HYPO-Rx group. The main outcomes studied were implantation rate, clinical pregnancy rate, clinical miscarriage rate, and live birth rate. Results: We reviewed the first IVF retrieval cycle performed on 240 women aged 37 years or less during the period January 2003 to December 2007. Women with treated hypothyroidism (n = 21) had significantly less implantation, clinical pregnancy, and live birth rates than euthyroid women (n = 219). Conclusions: We conclude that, despite levothyroxine treatment, women with hypothyroidism have a significantly decreased chance of achieving a pregnancy following IVF compared to euthyroid patients. A larger prospective study is necessary to assess confounding variables, confirm these findings, and determine the optimal level of TSH prior to and during controlled ovarian hyperstimulation for IVF

IGF1R Signaling Is Necessary for FSH-Induced Activation of AKT and Differentiation of Human Cumulus Granulosa Cells

CONTEXT: FSH is routinely administered to in vitro fertilization patients to induce follicle maturation. During this process, granulosa cells differentiate and acquire specific functional characteristics that are required to coordinate ovulation and oocyte maturation. OBJECTIVE: The objective of the study was to gain insight into the molecular mechanisms regulating human granulosa cell differentiation. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: Cumulus and mural granulosa cells were isolated from the follicular aspirates of in vitro fertilization patients and analyzed immediately or cultured in serum-free media in the presence of FSH, IGFs, or an inhibitor of type I IGF receptor (IGF1R) activity. MAIN OUTCOME: We quantified the mRNA and protein levels of steroidogenic enzymes, components of the IGF system, and gonadotropin receptors; measured 17β-estradiol levels; and examined the activation of intracellular signaling pathways to assess the granulosa cell differentiation as well as the FSH and IGF actions in both cumulus and mural cells. RESULTS: In freshly isolated cells, LH receptor (Lhr) and steroidogenic acute regulator (Star) were expressed at lower levels in cumulus than mural cells, whereas FSH receptor (Fshr) and anti-Müllerian hormone (Amh) were expressed at higher levels in cumulus than mural cells. In vitro, the expression of Igf2, the differentiation markers Lhr, Star, and Cyp19a1 (aromatase) as well as 17β-estradiol production remained low in untreated cumulus cells but increased significantly after FSH treatment. Strikingly, this stimulatory effect of FSH was abolished by the inhibition of IGF1R activity. FSH-induced activation of v-akt murine thymoma viral oncogene homolog 3 (AKT) required IGF1R activity, and overexpression of constitutively active AKT rescued the induction of differentiation markers and 17β-estradiol production by FSH in the presence of the IGF1R inhibitor. CONCLUSIONS: The cumulus cell response to FSH resembles the differentiation of preantral to preovulatory granulosa cells. This differentiation program requires IGF1R activity and subsequent AKT activation