How to deal with confounders in an infertility study?

Confounding variables represent one of the most important considerations for researchers and readers of scientific clinical papers.

The Appraisal of Body Content (ABC) trial: Increased male or female adiposity does not significantly impact in vitro fertilization laboratory or clinical outcomes.

Objective: To investigate the impact of obesity as determined by bioelectric impedance analysis (BIA) and body mass index (BMI) on in vitro fertilization (IVF) laboratory and clinical outcomes.

Design: Prospective cohort study.

Setting: Academic-affiliated private practice.

A multicenter, prospective, blinded, nonselection study evaluating the predictive value of an aneuploid diagnosis using a targeted next-generation sequencing-based preimplantation genetic testing for aneuploidy assay and impact of biopsy.

Objective: To determine the predictive value of an aneuploid diagnosis with a targeted next-generation sequencing-based preimplantation genetic testing for aneuploidy (PGT-A) assay in prognosticating the failure of a successful delivery.

Design: Prospective, blinded, multicenter, nonselection study. All usable blastocysts were biopsied, and the single best morphologic blastocyst was transferred before genetic analysis.

The appraisal of body content (ABC) trial: obesity does not significantly impact gamete production in infertile men and women.

Purpose: As obesity becomes increasingly prevalent, its impact on fertility has been a subject of great debate. Nearly all prior research is retrospective and evaluates obesity utilizing body mass index (BMI), which may overestimate adiposity in individuals with a greater amount of lean muscle and underestimate adiposity in those with less muscle mass.

Methods: We prospectively evaluated 2013 couples undergoing infertility treatment with in vitro fertilization (IVF).

Three-dimensional ultrasound diagnosis of adenomyosis is not associated with adverse pregnancy outcome following single thawed euploid blastocyst transfer: prospective cohort study.

Objectives: The objectives of this study were (1) to assess the prevalence of ultrasound (US) features of adenomyosis in an infertile population undergoing in-vitro fertilization (IVF), (2) to define the inter- and intrarater agreement of three-dimensional (3D) US assessment of adenomyosis, and (3) to evaluate sonographic features of adenomyosis with respect to pregnancy outcome following transfer of a single thawed euploid blastocyst.

Methods: This was a prospective cohort study. Subjects scheduled to undergo a single thawed euploid blastocyst transfer between April and December 2017 at a large IVF center were eligible for inclusion.

Embryo's Natural Motion (enMotion): a paired randomized controlled trial evaluating a dynamic embryo culture system.

Objective: To determine if a dynamic embryo culture system affects the reproductive potential of human embryos resulting from in vitro fertilization (IVF).

Design: Paired randomized controlled trial (RCT).

Setting: IVF center.

Embryonic aneuploidy rates are equivalent in natural cycles and gonadotropin-stimulated cycles.

Objective: To determine if natural selection and follicular stimulation produces a lower risk for embryonic aneuploidy than that attained following superovulation with exogenous gonadotropins.

Design: Prospective observational with historical control group.

Setting: Large academically affiliated private practice.

Worth the wait? Day 7 blastocysts have lower euploidy rates but similar sustained implantation rates as Day 5 and Day 6 blastocysts.

Study Question: Does the reproductive potential of embryos change when blastocyst development takes longer than the traditionally accepted 5 days when accounting for aneuploidy and endometrial-embryo asynchrony?

Summary Answer: Aneuploidy increases with increasing duration of blastulation, but if blastocyst morphologic quality and endometrial-embryo asynchrony are controlled for, euploid Day 7 embryos have similar sustained implantation as compared to Days 5 and 6 euploid blastocysts.

What Is Known Already: The relative contributions of diminished embryo quality versus endometrial and embryo asynchrony to poor outcomes associated with embryos cultured past Day 6 are not clear. Asynchrony can be eliminated by embryo vitrification with transfer in a subsequent month after retrieval.

Investigating the impact of the timing of blastulation on implantation: management of embryo-endometrial synchrony improves outcomes.

Study Question: Do embryos with delayed blastulation have inferior reproductive potential or poorer outcomes due in part to embryo and endometrial synchrony?

Summary Answer: Diminished outcomes in embryos with delayed blastulation undergoing fresh embryo transfer (ET) may be attributed to a loss of embryonic-endometrial synchrony.

What Is Known Already: Embryos that blastulate slowly have lower sustained implantation rates (SIR) than those which blastulate normally on Day 5 (D5). Traditionally this has been attributed to reduced embryo quality; however, dyssynchrony with the endometrium is also a possibility and has not been fully described.

Diminished ovarian reserve and poor response to stimulation in patients <38 years old: a quantitative but not qualitative reduction in performance.

Study Question: Do infertile women aged <38 years with quantitative evidence of diminished ovarian reserve and/or poor response to stimulation also exhibit poor oocyte quality as measured by blastulation rates, aneuploidy rates, and live birth rates?

Summary Answer: Young women with evidence of accelerated follicular depletion, either by precycle ovarian reserve testing or postcycle evidence of low oocyte yield, exhibit equivalent blastulation rates, aneuploidy rates and live birth rates per euploid embryo transfer as age-matched controls with normal precycle and postcycle parameters.

What Is Known Already: Previous studies are conflicted as to whether women with evidence of diminished ovarian reserve and/or poor ovarian response are also at increased risk of exhibiting evidence of poor oocyte quality. Most prior studies have failed to adequately control for the confounding effect of female age on typical markers of oocyte quality in poor responders.

Complexities and potential pitfalls of clinical study design and data analysis in assisted reproduction.

Purpose Of Review: The purpose of the current review is to describe the common pitfalls in design and statistical analysis of reproductive medicine studies. It serves to guide both authors and reviewers toward reducing the incidence of spurious statistical results and erroneous conclusions.

Recent Findings: The large amount of data gathered in IVF cycles leads to problems with multiplicity, multicollinearity, and over fitting of regression models.

Characterization of reproductive endocrinology and infertility (REI) fellowship applicants: guiding our mentees toward success.

Background: Advanced subspecialty training in reproductive endocrinology and infertility (REI) entails a competitive application process with many data points considered. It is not known what components weigh more heavily for applicants. Thus, we sought to study the REI fellow applicant and compare 1) those who apply but do not receive an interview, 2) those who receive an interview but do not match, and 3) those who successfully match.

Diminished ovarian reserve as measured by means of baseline follicle-stimulating hormone and antral follicle count is not associated with pregnancy loss in younger in vitro fertilization patients.

Objective: To assess the relationship between diminished ovarian reserve and pregnancy outcomes in a large cohort of women achieving pregnancy through in vitro fertilization (IVF). We evaluated antral follicle count (AFC) and baseline FSH as a measure of ovarian reserve. Secondarily, we assessed whether diminished ovarian reserve was associated with aneuploidy among spontaneous abortions.

Patients with endometriosis have aneuploidy rates equivalent to their age-matched peers in the in vitro fertilization population.

Objective: To determine whether endometriosis ultimately results in an increased risk of embryonic aneuploidy.

Design: Retrospective cohort.

Setting: Infertility clinic.

Does premature elevated progesterone on the day of trigger increase spontaneous abortion rates in fresh and subsequent frozen embryo transfers?

Recent evidence has shown elevated progesterone (P) advances the endometrium in fresh ART cycles, creating asynchrony with the embryo and thus implantation failure and decreased live birth rates. If the window of implantation is closing as the embryo attempts to implant, there may be difficulty with trophoblastic invasion, leading to failure of early pregnancies. Our objective was to evaluate if P on the day of trigger was associated with spontaneous abortion (SAB) rates in fresh ART transfers.

Revisiting the progesterone to oocyte ratio.

Objective: To critically evaluate the P to oocyte (O) ratio (P/O) in the prediction of live birth in assisted reproductive technology (ART) cycles.

Design: Retrospective cohort study.

Setting: Not applicable.

The slow growing embryo and premature progesterone elevation: compounding factors for embryo-endometrial asynchrony.

Study Question: Is there an association of progesterone (P) on the day of trigger with live birth in autologous ART transfer cycles on day 5 versus day 6?

Summary Answer: P had a greater negative effect on live birth in day 6 fresh transfers compared to day 5 fresh transfers.

What Is Known Already: Premature P elevation is associated with lower live birth rates in fresh autologous ART cycles, likely due to worsened endometrial-embryo asynchrony. Few studies have evaluated whether the effect of an elevated P on the day of trigger is different on live birth rates with a day 5 compared to a day 6 embryo transfer.