In women, anti-Müllerian hormone (AMH) levels may represent the ovarian follicular pool and could be a useful marker of ovarian reserve. The clinical application of AMH measurement has been proposed in the prediction of quantitative and qualitative aspects in assisted reproductive technologies (ART). In men AMH is secreted in both the serum and seminal fluid. Its measurement may be useful in clinical evaluation of the infertile male.
The PubMed database was systematically searched for studies published until the end of January 2009, search criteria relevant to AMH, ovarian reserve, ovarian response to gonadotrophin stimulation, spermatogenesis and azoospermia were used.
AMH seems to be a better marker in predicting ovarian response to controlled ovarian stimulation than age of the patient, FSH, estradiol and inhibin B. A similar performance for AMH and antral follicular count has been reported. In clinical practice, AMH measurement may be useful in the prediction of poor response and cycle cancellation and also of hyper-response and ovarian hyperstimulation syndrome. In the male, the wide overlap of AMH values between controls and infertile men precludes this hormone from being a useful marker of spermatogenesis.
As AMH may permit the identification of both the extremes of ovarian stimulation, a possible role for its measurement may be in the individualization of treatment strategies in order to reduce the clinical risk of ART along with optimized treatment burden. It is fundamental to clarify the cost/benefit of its use in ovarian reserve testing. Regarding the role of AMH in the evaluation of infertile men, AMH as single marker of spermatogenesis does not seem to reach a satisfactory clinical utility.
Bilateral oophorectomy is commonly performed at the time of hysterectomy for benign disease. Indications for oophorectomy vary, but in most cases relatively little high-quality information is available to inform the surgeon or patient regarding the relative risks and benefits of ovarian conservation or removal. This review will address the common clinical situations when oophorectomy may be performed and will evaluate the evidence for risk and benefit in each of these circumstances. The aim of this review is to bring together the evidence regarding oophorectomy in pre- and post-menopausal women and to highlight the areas needing further study.
We searched the published literature for studies related to outcomes following surgical menopause, risk-reducing surgery for ovarian cancer, surgical treatment for endometriosis, bilateral oophorectomy for benign disease and treatment for premenstrual syndrome/premenstrual dysphoric disorder.
Rates of oophorectomy at the time of hysterectomy for benign disease appear to be increasing. There is good evidence to support bilateral salpingoophorectomy (BSO) as a risk-reducing surgery for women at high risk of ovarian cancer, but relatively little evidence to support oophorectomy or BSO in other circumstances. There is growing evidence from observational studies that surgical menopause may impact negatively on future cardiovascular, psychosexual, cognitive and mental health.
Clinicians and patients should fully consider the relative risks and benefits of oophorectomy on an individual basis prior to surgery.
microRNAs (miRNAs) are short, single-stranded RNAs that regulate gene expression at the post-transcriptional level. Recent research has shown that miRNAs and their target mRNAs are differentially expressed in endometriosis and other disorders of the female reproductive system. Since miRNAs control a broad spectrum of normal and pathological cellular functions, they may play pivotal roles in the pathogenesis of these disorders.
A systematic review was undertaken of the published literature on; (i) the expression and functions of miRNAs in mammalian female reproductive tissues with a focus on endometriosis and the malignancies and fertility disorders related to this disease; and (ii) the potential roles played by validated mRNA targets of endometriosis-associated miRNAs. The current understanding of the biology of miRNAs is overviewed and the potential diagnostic and therapeutic potential of miRNAs in endometriosis is highlighted.
The differential expression of miRNAs in endometriosis, and the putative molecular pathways constituted by their targets, suggests that miRNAs may play an important role in endometriotic lesion development. Models for miRNA regulatory functions in endometriosis are presented, including those associated with hypoxia, inflammation, tissue repair, TGFβ-regulated pathways, cell growth, cell proliferation, apoptosis, extracellular matrix remodelling and angiogenesis. In addition, specific miRNAs which may be associated with malignant progression and subfertility in endometriosis are discussed.
miRNAs appear to be potent regulators of gene expression in endometriosis and its associated reproductive disorders, raising the prospect of using miRNAs as biomarkers and therapeutic tools in endometriosis.
Preimplantation embryos are particularly susceptible to in vitro developmental blocks. These could be alleviated by lowering culture medium osmolarity. Because mammalian cells regulate their volumes by adjusting intracellular osmotic pressure, cell volume regulation could be critical to early embryos.
We reviewed the literature on cell volume regulation in preimplantation embryos and the effects of increased osmolarity on embryo development, focusing also on the relation with improvements in embryo culture media.
Embryos failed to develop from fertilized oocytes when osmolarity is increased. This could be alleviated by decreasing osmolarity or including certain compounds such as certain amino acids. Early preimplantation mouse embryos require intracellular accumulation of glycine to provide osmotic support and thus control cell volume. The glycine-specific transporter, GLYT1, mediates osmoregulated glycine accumulation in mouse embryos and likely in human embryos. GLYT1 is activated during meiotic maturation starting at ovulation. Prior to this, oocyte size is not independently controlled but instead is determined by strong adhesion between the oocyte plasma membrane and the inner surface of the zona pellucida.
Early preimplantation embryos are particularly sensitive to increased osmolarity, and require the importation of glycine to regulate their cell volumes using a mechanism unique to early embryos. Cell volume regulation first appears when ovulation is triggered, oocyte zona pellucida adhesion is released, and glycine transport is activated. The requirement for supporting these physiological functions in oocytes and embryos should be taken into account when developing and improving systems for in vitro oocyte maturation and embryo culture.
Hypergonadotropic hypoestrogenic infertility is the most burdensome complication for females suffering from classic galactosemia. In contrast, male gonadal function seems less affected. The underlying mechanism is not understood and several pathogenic mechanisms have been proposed. Timing of the lesion, prenatal or chronic post-natal, or a combination of both are not yet clear.
This review focuses on gonadal function in males and females, ovarian imaging and histology in this disease. It is based on the literature known to the authors and a Pubmed search using the keywords galactosemia, GALT deficiency, (premature) ovarian failure/insufficiency/dysfunction, testicular function, gonadotrophins, FSH, LH (published between January 1971 and April 2009).
Male gonads are less affected, boys spontaneously reach puberty, although onset can be delayed. Semen quality has not been extensively studied. Several affected males are known to have fathered a child. Female gonads are invariably affected, although to a varied extent (hypergonadotropic hypoestrogenic ovarian dysfunction). Intriguingly, FSH is often already increased in infancy. Imaging usually shows hypoplastic and streak-like ovaries. Histological findings in some cases reveal the presence of morphologically normal but decreased numbers of primordial follicles, with the absence of intermediate and Graafian follicles.
Gonads in males seem less affected than in females who exhibit hypergonadotropic hypoestrogenic subfertility. FSH can be elevated in infancy, and ovarian histology sometimes shows the presence of normal primordial follicles with absence of intermediate and Graafian follicles. These findings are similar to other genetic diseases primarily affecting the ovary.
The majority of Chlamydia trachomatis infections in women are asymptomatic, but may give rise to pelvic inflammatory disease (PID) and tubal infertility. Screening programmes aim at reducing morbidity in individuals by early detection and treatment, and at decreasing the overall prevalence of infection in the population. A number of modelling studies have tried to calculate the threshold prevalence of chlamydia lower genital tract infection above which screening becomes cost-effective. There is considerable debate over the exact complication rates after chlamydia infections, and more precise estimates of PID and tubal infertility are needed, for instance to be inserted in economic models.
With reference to key studies and systematic reviews, an overview is provided focusing on the epidemiology of chlamydia infection and the risk-estimates of its late complications.
In the literature, the generally assumed risk of developing PID after lower genital tract chlamydia infection varies considerably, and is up to 30%. For developing tubal infertility after PID the risks are 10–20%. This implies that the risk of test-positive women of developing tubal infertility would range between 0.1 and 6%. We included chlamydia IgG antibody testing in a model and estimated a risk of tubal infertility up to 4.6%.
The risk of developing late complications after chlamydia lower genital tract infection appears low. High quality RCTs dealing with the transition from cervicitis to infertility are needed to broaden the evidence. In screening programmes, chlamydia antibody testing, as an intermediate marker for potential adverse sequelae, might enable more precise estimates.
Functional male gametes are produced through complex processes that take place within the testis, epididymis and female reproductive tract. A breakdown at any of these phases can result in male infertility. The production of mutant mouse models often yields an unexpected male infertility phenotype. It is with this in mind that the current review has been written. The review aims to act as a guide to the ‘non-reproductive biologist’ to facilitate a systematic analysis of sterile or subfertile mice and to assist in extracting the maximum amount of information from each model.
This is a review of the original literature on defects in the processes that take a mouse spermatogonial stem cell through to a fully functional spermatozoon, which result in male infertility. Based on literature searches and personal experience, we have outlined a step-by-step strategy for the analysis of an infertile male mouse line.
A wide range of methods can be used to define the phenotype of an infertile male mouse. These methods range from histological methods such as electron microscopy and immunohistochemistry, to hormone analyses and methods to assess sperm maturation status and functional competence.
With the increased rate of genetically modified mouse production, the generation of mouse models with unexpected male infertility is increasing. This manuscript will help to ensure that the maximum amount of information is obtained from each mouse model and, by extension, will facilitate the knowledge of both normal fertility processes and the causes of human infertility.