Maternal serum concentration of anti-Müllerian hormone is a better predictor than basal follicle stimulating hormone of successful blastocysts development during IVF treatment.

BACKGROUND: The conditions of diminished ovarian reserve and primary ovarian insufficiency, characterized by poor fertility outcomes, currently comprise a major challenge in reproductive medicine, particularly in vitro fertilization. Currently in the IVF industry, blastocyst developmental success rate per treatment is routinely overlooked when a live birth results from treatment. Limited data are available on this significant and actionable variable of blastocyst development optimization, which contributes to improvement of treatment success Women with elevated basal FSH concentration are reported to still achieve reasonable pregnancy rates, although only a few studies report correlations with blastocysts development. Diagnostic values of AMH/basal FSH concentrations can be useful for determining the optimal stimulation protocol as well as identification of individuals who will not benefit from IVF due to poor prognosis. The objective of this study is to identify actionable clinical and culture characteristics of IVF treatment that influence blastocyst developmental rate, with the goal of acquiring optimal success. METHODS AND FINDINGS: A retrospective observational study was performed, based on 106 women undergoing IVF, regardless of prognosis, over a six-month period from January 1, 2015 to June 31, 2015. Rate of high-quality blastocyst production, which can be used for embryo transfer or vitrification, per normally fertilized oocyte, was evaluated. Treatment was determined successful when outcome was ≥ 40% high-quality blastocysts. The data were initially evaluated with the Evtree algorithm, a statistical computational analysis which is inspired by natural Darwinian evolution incorporating concepts such as mutation and natural selection (see Supplementary Material). The analysis processes all variables simultaneously against the outcome, aiming to maximize discrimination of each variable to then create a "branch" of the tree which can be used as a decision in treatment. The final model results in only those variables which are significant to outcomes. Generalized linear model (GLM) employing logistic regression and survival analysis with R software was used and the final fitting of the model was determined through the use of random forest and evolutionary tree algorithms. Individuals presenting with an [AMH] of >3.15 ng/ml and a good prognosis had a lower success per treatment (n = 11, 0% success) when total gonadotropin doses were greater than 3325 IU. Individuals that presented with an [AMH] of <1.78 ng/ml and a poor prognosis exhibited a greater success per treatment (n = 11, 80% success). AMH emerged as a superior indicator of blastocyst development compared to basal FSH. The accuracy of the prediction model, our statistical analysis using decision tree, evtree methodology is 86.5% in correctly predicting outcome based on the significant variables. The likelihood that the outcome with be incorrect of the model, or the error rate is 13.5%. CONCLUSIONS: [AMH] is a superior indicator of ovarian stimulation response and an actionable variable for stimulation dose management for optimizing blastocyst development in culture. Women whose [AMH] is ≥3.2 mg/ml, having a good prognosis, and developing >12 mature follicles result in <40% blastocysts when gonadotropin doses exceed 3325 IU per treatment. IVF treatments for poor responders that present with infertility due to diminished ovarian reserve, if managed appropriately, can produce more usable blastocyst per IVF treatment, thus increasing rate of blastocyst developmental success and ultimately increasing live birth rates. Future studies are needed to investigate the intra-follicular and the intra-cellular mechanisms that lead to the inverse relationship of blastocysts development and total gonadotropin doses in good responders in contrast to poor responders.

Intermedin/adrenomedullin 2 is associated with implantation and placentation via trophoblast invasion in human pregnancy.

RATIONALE: Intermedin (IMD) is a novel peptide expressed in trophoblast cells in human placenta and enhances the invasion, migration, and human leukocyte antigen class I, G (HLA-G) expression in first-trimester HTR-8SV/neo cells. We recently reported that infusion of IMD antagonist in pregnant rats is detrimental to pregnancy outcome, resulting in impaired fetoplacental growth and deformed placental vasculature. OBJECTIVE: This study was undertaken to assess expression of IMD and its involvement in human implantation and early placentation and assess whether its expression is altered in spontaneous abortion. FINDINGS AND CONCLUSIONS: We demonstrate for the first time that IMD is present in day 5 embryonic secretome; villous and decidual expression of IMD is higher at 6-8 weeks after a decline as gestation advances toward the second trimester; first-trimester spontaneous abortion is associated with a lower expression of IMD in serum, villi, and decidua; IMD stimulates the invasive capacity of first-trimester primary Extravillous cytotrophoblast cells; and IMD decreases elevated levels of tumor suppressor Kangia-1 in decidual explants from first-trimester spontaneous abortion. In conclusion, this study is the first to demonstrate a potential involvement of IMD in human embryo implantation and placental development via regulation of trophoblast invasion at the maternal-fetal interface and suggests a physiological role for this novel peptide in establishment of human pregnancy.

Avoiding legal pitfalls in surrogacy arrangements.

The goal of this article is to discuss the legal pitfalls that reproductive endocrinologists face when participating in gestational surrogacy contracts. This paper was composed using Westlaw and LexisNexis commercial legal search engines to perform a review of statutes and cases pertaining to gestational surrogacy. The search results demonstrated that in the absence of suitable preparation, there is significant potential for litigation while participating in gestational agreements. Providers caring for gestational carriers have been named as parties in lawsuits for failure to provide psychological screening, failure to screen for infectious disease and participation in gestational contracts that are not compliant with state law. There is great disparity in state laws and court rulings pertaining to gestational agreements. When legal disputes arise, individual state laws and court rulings are controlling over the Uniform Parentage Act. Likewise, recommendations by the American College of Obstetricians and Gynecologists and the American Society for Reproductive Medicine do not supersede state laws. The failure to abide by individual state laws unnecessarily exposes reproductive endocrinologists and their IVF facilities to potential litigation. In order to lessen exposure to litigation, an understanding of individual state legislation or historical court rulings is advised.

Reproduction beyond menopause: how old is too old for assisted reproductive technology?

BACKGROUND: Due to the recent media attention on postmenopausal women giving birth, there has been an increased scrutiny on the utility and safety of assisted reproductive technology in postmenopausal women. OBJECTIVE: The purpose of this commentary is to discuss the following: 1) the limitations and complications of ART in women of advanced reproductive age; 2) the balance between the welfare of the mother and that of the child; 3) the double standards of advanced reproductive age; and 4) the importance of financial and social support systems and preconception counseling with advanced reproductive age. CONCLUSION: When providing in-vitro fertilization services to women of advanced reproductive age, special considerations must be given to ensure the welfare of mother and the child and that the principles of beneficence and nonmaleficence are guaranteed.