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Category Archives: Human Reproduction

Karyotype of miscarriages in relation to maternal weight

BACKGROUND

Obesity has been identified as a risk factor for spontaneous miscarriage although the mechanism is unclear. The purpose of this study is to better understand the effect of obesity on early pregnancy success by examining the cytogenetic results of miscarriages in women with normal and elevated body mass index (BMI).

METHODS

We conducted a retrospective case–control study in an academic infertility practice. Medical records of women ages <40 years with first trimester missed abortion (n = 204), who underwent dilatation and curettage between 1999 and 2008, were reviewed for demographics, BMI, diagnosis of polycystic ovary syndrome (PCOS) and karyotype analysis. 2 and Student's t-test analysis were used for statistical analysis, with P < 0.05 considered significant.

RESULTS

A total of 204 miscarriages were included, from women with a mean age of 34.5 years. The overall rate of aneuploidy was 59%. Women with BMI ≥ 25 kg/m2 had a significant increase in euploid miscarriages compared with women with lower BMI (P = 0.04), despite a similar mean age (34.4 years for both).

CONCLUSIONS

We found a significant increase in normal embryonic karyotypes in the miscarriages of overweight and obese women (BMI ≥ 25). These results suggest that the excess risk of miscarriages in the overweight and obese population is independent of embryonic aneuploidy. Further studies are needed to assess the impact of lifestyle modification, insulin resistance and PCOS on pregnancy outcomes in the overweight and obese population.

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Xenografting of testicular tissue from an infant human donor results in accelerated testicular maturation

BACKGROUND

Grafting of testicular tissue into immunodeficient mice has been used to differentiate the neonatal testes from different animal species up to the level of complete spermatogenesis; however, this approach has not been successful for human testicular tissue. The aim of this study was to evaluate the capacity for differentiation of infant human testicular tissue grafts.

METHODS AND RESULTS

Testicular tissue from a 3-month-old patient with testicular cancer was grafted into immunodeficient nude mice. At the time of grafting, A spermatogonia were the only germ cells present in the testicular tissue. B spermatogonia and first spermatocytes were observed at 7 months and 1 year after grafting, respectively. Positive immunostaining with antibodies against BOULE and CDC25A suggested that spermatocytes in the graft were not arrested but in meiosis. Furthermore, ultrastructural and immunohistochemical analyses showed that the onset of both Sertoli cell maturation and partial differentiation of Leydig cells preceded the appearance of spermatocytes. Differentiation of testicular cells was accelerated compared with in vivo development.

CONCLUSIONS

Spermatogenesis in the xenograft of infant human testicular tissues proceeded successfully from the stage of spermatogonial stem cells until pachytene spermatocyte formation. The differentiation of Sertoli cells and Leydig cells was reproduced in a manner similar to that in normal testicular development. Grafting of infant human testicular tissue may be a powerful tool to examine the early period of human spermatogenesis and may pave the way for fertility preservation among infant patients.

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World Health Organization reference values for human semen characteristics

BACKGROUND

Semen quality is taken as a surrogate measure of male fecundity in clinical andrology, male fertility, reproductive toxicology, epidemiology and pregnancy risk assessments. Reference intervals for values of semen parameters from a fertile population could provide data from which prognosis of fertility or diagnosis of infertility can be extrapolated.

METHODS

Semen samples from over 4500 men in 14 countries on four continents were obtained from retrospective and prospective analyses on fertile men, men of unknown fertility status and men selected as normozoospermic. Men whose partners had a time-to-pregnancy (TTP) of ≤12 months were chosen as individuals to provide reference distributions for semen parameters. Distributions were also generated for a population assumed to represent the general population.

RESULTS

The following one-sided lower reference limits, the fifth centiles (with 95th percent confidence intervals), were generated from men whose partners had TTP ≤ 12 months: semen volume, 1.5 ml (1.4–1.7); total sperm number, 39 million per ejaculate (33–46); sperm concentration, 15 million per ml (12–16); vitality, 58% live (55–63); progressive motility, 32% (31–34); total (progressive + non-progressive) motility, 40% (38–42); morphologically normal forms, 4.0% (3.0–4.0). Semen quality of the reference population was superior to that of the men from the general population and normozoospermic men.

CONCLUSIONS

The data represent sound reference distributions of semen characteristics of fertile men in a number of countries. They provide an appropriate tool in conjunction with clinical data to evaluate a patient's semen quality and prospects for fertility.

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Options for fertility preservation in prepubertal boys

BACKGROUND

Fertility in adult life may be severely impaired by gonadotoxic therapies. For young boys who do not yet produce spermatozoa, cryopreservation of immature testicular tissue (ITT) is an option to preserve their fertility, albeit still experimental. This paper covers current options for ITT cryopreservation and fertility restoration.

METHODS

Relevant studies were identified by an extensive Medline search of English and French language articles. Search terms were: gonadotoxicity, cytoprotection, cryopreservation, ITT, spermatogonia, testicular transplantation, testicular grafting and in vitro maturation (IVM).

RESULTS

Although no effective gonadoprotective drug is yet available for in vivo spermatogonial stem cell protection in humans, current evidence supports the feasibility of ITT cryopreservation before gonadotoxic treatment with a view to fertility preservation. Controlled slow freezing with dimethyl sulfoxide allows survival and proliferation of human spermatogonia after xenotransplantation, but only partial differentiation. Animal data look promising, since healthy offsprings have been obtained after transplantation of frozen testicular cell suspensions or tissue pieces. However, none of the fertility restoration options from frozen tissue, i.e. cell suspension transplantation, tissue grafting and IVM have proved efficient and safe in humans as yet.

CONCLUSION

While additional evidence is required to define optimal conditions for ITT cryopreservation with a view to transplantation or IVM, the putative indications for such techniques, as well as their limitations according to disease, are outlined.

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The impact of body mass index on semen parameters and reproductive hormones in human males: a systematic review with meta-analysis

BACKGROUND

It has been suggested that body mass index (BMI), especially obesity, is associated with subfertility in men. Semen parameters are central to male fertility and reproductive hormones also play a role in spermatogenesis. This review aimed to investigate the association of BMI with semen parameters and reproductive hormones in men of reproductive age.

METHODS

MEDLINE, EMBASE, Biological Abstracts, PsycINFO and CINAHL databases and references from relevant articles were searched in January and February 2009. Outcomes included for semen parameters were sperm concentration, total sperm count, semen volume, motility and morphology. Reproductive hormones included were testosterone, free testosterone, estradiol, FSH, LH, inhibin B and sex hormone binding globulin (SHBG). A meta-analysis was conducted to investigate sperm concentration and total sperm count.

RESULTS

In total, 31 studies were included. Five studies were suitable for pooling and the meta-analysis found no evidence for a relationship between BMI and sperm concentration or total sperm count. Overall review of all studies similarly revealed little evidence for a relationship with semen parameters and increased BMI. There was strong evidence of a negative relationship for testosterone, SHBG and free testosterone with increased BMI.

CONCLUSIONS

This systematic review with meta-analysis has not found evidence of an association between increased BMI and semen parameters. The main limitation of this review is that data from most studies could not be aggregated for meta-analysis. Population-based studies with larger sample sizes and longitudinal studies are required.

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Brain imaging studies of appetite in the context of obesity and the menstrual cycle

BACKGROUND

Obesity affects many aspects of health, including reproduction. Despite unrelenting warnings about the health consequences of obesity, its prevalence continues to rise. Beginning with the discovery of leptin in 1994, the endocrinology of energy homeostasis has been significantly advanced. More recently, brain imaging studies have been providing novel insights into homeostatic and hedonic aspects of human ingestive behavior.

METHODS

A comprehensive MEDLINE search was conducted on the topic of neuroendocrine control of ingestive behavior with an emphasis on functional magnetic resonance imaging studies. Additional articles were collected by hand searching the bibliographies of all relevant articles retrieved.

RESULTS

This review describes recent advances in our understanding of endocrine signals that respond to acute and chronic energy states and regulate ingestive behavior so as to achieve a balance between energy intake and energy expenditure. Recently published brain imaging studies, describing the neural networks that process endocrine signals of energy state and hedonic cues associated with highly palatable foods, are highlighted. Brain responses to food cues are described in the context of appetite changes during the menstrual cycle both in normal physiology and under the conditions anorexia nervosa and bulimia nervosa.

CONCLUSIONS

The prevalence of obesity belies the plethora of endocrine signals in place to ensure energy homeostasis. However, satiety signals appear to be counteracted by hedonic signals derived from highly palatable foods typical of today's diet. A better understanding of the interaction between homeostatic and hedonic signals is needed to devise effective strategies for dealing with obesity. Menstrual cycle dependent changes in brain responses to food cues may provide insight into the normal physiological control of ingestive behavior as well as dysfunctional regulation associated with disordered eating.

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