L. Pal

Age-related decline in fertility

A progressive decline in fecundity with advancing age is a reality, attributed primarily to the detrimental impact of various aging processes on female gametes. Despite medical advances that have dramatically prolonged the female life span, declining numbers and deteriorating quality of oocytes, and an increasing incidence of meiotic errors and aneuploidy of gametes and embryos, reduce clinical pregnancy rates and escalate pregnancy wastage. Increased fetal aneuploidies in ongoing pregnancies and an increased predisposition to obstetric morbidities further contribute to the diminishing reproductive successes associated with advancing age. The age of male partners, despite the decline in semen parameters and sexual performance with aging, does not appear to have a major impact on the eventual fertility of the aging couple. The contributions of age-related impaired sexuality and ejaculatory problems, although slight albeit significant, to declining fertility in the aging should be appreciated in appropriate cases. With the realization of the age-related detriment on fertility potential and the limitations of available therapeutic interventions, management of subfecundity in women beyond their mid-30s should be approached aggressively. Success of ovulation induction with clomiphine citrate or gonadotropins is marginal in women aged older than 40 years; a case can be made to proceed directly with ART in women in this age group, especially when there is coexisting male factor or pelvic disease. Except for the use of donor oocytes, the outcome of various therapeutic interventions to optimize reproductive performance in women aged older than 44 years remains dismal. A broader application of PGD techniques may contribute to improved live birth rates in reproductively aging women. The greater likelihood of obstetric complications in pregnancies resulting from donor oocytes and an increased prevalence of age-related medical problems complicating pregnancy should prompt a thorough medical evaluation before proceeding with ART.

Less is more: increased gonadotropin use for ovarian stimulation adversely influences clinical pregnancy and live birth after in vitro fertilization

OBJECTIVE To determine if attempts to maximize oocyte yield during ovarian stimulation translates into improved outcome of in vitro fertilization (IVF) cycles. DESIGN Retrospective study. SETTING Academic tertiary care IVF center. PATIENT(S) 806 de-identified nondonor IVF cycles. INTERVENTION(S) Evaluation of fresh nondonor IVF cycles (n = 806) for the period January 1, 1999, to December 30, 2001. MAIN OUTCOME MEASURE(S) Cycle cancellation, clinical pregnancy, spontaneous miscarriage, and live birth after IVF. RESULT(S) Advancing age, independent of ovarian reserve status (reflected by early follicular phase FSH and estradiol) augured a worse prognosis for all outcomes. Higher gonadotropin use lowered cycle cancellations but was associated with a statistically significantly reduced likelihood of clinical pregnancy and live birth and a trend toward a higher likelihood for spontaneous miscarriage after IVF. CONCLUSION(S) Our data add to the accruing literature suggesting adverse influences of excess gonadotropin use on IVF outcomes. Although an aggressive approach to controlled ovarian hyperstimulation results in a statistically significant reduction in cycle cancellations, the excessive use of gonadotropins detrimentally influences live birth after IVF.

Premature ovarian failure (POF): discordance between somatic and reproductive aging.

Premature ovarian failure (POF) is a unique example of isolated organ senescence, with a population prevalence of approximately 1%. Though the phenotypic expression of POF is similar to that of age-appropriate natural menopause, the underlying pathophysiological mechanisms are diverse and not entirely clear. The impact of POF on the patient is profound, with myriad ramifications, ranging from psychological devastation to multi-system implications of estrogen deprivation and its sequelae. The hastening of degenerative changes noted in these patients however, are not entirely ameliorated with estrogen replacement and POF may indeed represent an acceleration of the aging process.

Declining ovarian reserve adversely influences granulosa cell viability

OBJECTIVE To identify if declining ovarian reserve adversely influences granulosa cell (GC) parameters in patients undergoing IVF. DESIGN Prospective study. SETTING Academic IVF Center. PATIENT(S) Twenty-four women undergoing IVF. INTERVENTION(S) Mural and cumulus GCs were harvested (at time of egg retrieval). MAIN OUTCOME MEASURE(S) Influence of ovarian reserve, reflected by maximal basal FSH levels, on GC (cumulative, mural, and cumulus) counts and viability were investigated. RESULT(S) The FSH levels demonstrated an inverse correlation with cumulative and mural, but not cumulus, GC viability. Adverse influence of increasing FSH on cumulative GC viability was independent of patients age. The GC counts were uninfluenced by ovarian reserve status. Neither GC count nor viability demonstrated any relationship with clinical pregnancy after IVF. CONCLUSION(S) We observed an adverse association between declining ovarian reserve and GC parameters. We believe these findings may partly explain the suboptimal reproductive performance in these women.

Effect of Weight Loss by Bariatric Surgery on the Risk of Miscarriage

The aim of this paper is to appraise the literature with a view to establish whether weight loss by bariatric surgery has a beneficial effect on lowering the risk of miscarriage in morbidly obese women. Literature review revealed that weight loss by bariatric surgery on miscarriage rate has not been studied enough.

Reproductive implications of psychological distress for couples undergoing IVF

ObjectiveTo study implications of psychological distress on in vitro fertilization (IVF) outcome of an infertile couple.MethodsProspective study in an academic infertility practice setting. Couples undergoing embryo transfer (ET) following IVF were offered participation. Female patient (n = 89) and partner (n = 77) completed questionnaires reflecting dysphoria (POMS) and pessimism (LOT) after undergoing ET. Relationship between dysphoria and pessimism and implications of individual and couple’s psychological distress on IVF cycle parameters and outcomes were assessed using multivariable analyses.ResultsStatistically significant correlations between dysphoria and pessimism were observed within the individual and between partners, (p < 0.01). Higher couple pessimism correlated with longer duration of controlled ovarian hyperstimulation (COH, p = 0.02); higher partner psychological distress related to lower fertilization rate (FR, p = 0.03). On adjusted analyses, partner’s depression score was an independent predictor of reduced likelihood of clinical pregnancy (p = 0.03).ConclusionsOur data validate the concept of a “stressed couple”. Adverse implications of a couple’s psychological distress for gamete biology (longer duration of COH and lower FR with increasing distress) are suggested. Partner’s depressive scores negatively correlated with IVF success. These findings suggest the importance of including partner’s evaluation in studies that focus on effects of psychological stress on IVF outcome; future studies should examine whether interventions aimed at reducing psychological stress for the infertile couple may improve IVF cycle success.

Gender “tailored” conceptions: should the option of embryo gender selection be available to infertile couples undergoing assisted reproductive technology?

The purpose of this article is to ascertain and appraise the ethical issues inherent to the utilisation of preimplantation genetic diagnosis for gender selection in infertile patients anticipating undergoing a medically indicated assisted reproductive technique procedure. Performance of preimplantation genetic diagnosis per request specifically for gender selection by an infertile couple undergoing medically indicated assisted reproductive technique may not breach the principles of ethics, and is unlikely to alter the population balance of sexes.