Category Archives: Human Reproduction

BACKGROUND

Uterine contractile activity plays an important role in many and varied reproductive functions including sperm and embryo transport, implantation, menstruation, gestation and parturition. Abnormal contractility might underlie common and important disorders such as infertility, implantation failure, dysmenorrhea, endometriosis, spontaneous miscarriage or preterm birth.

METHODS

A systematic review of the US National Library of Medicine was performed linking ‘uterus’ or ‘uterine myocyte’ with ‘calcium ion’ (Ca²⁺), ‘myosin light chain kinase’ and ‘myosin light chain phosphatase’. This led to many cross-references involving non-uterine myocytes and, where relevant, these data have been incorporated into the following synthesis.

RESULTS

We have grouped the data according to three main components that determine uterine contractility: the contractile apparatus; electrophysiology of the myocyte including excitation-contraction coupling; and regulation of the sensitivity of the contractile apparatus to Ca²⁺. We also have included information regarding potential therapeutic methods for regulating uterine contractility.

CONCLUSIONS

More research is necessary to understand the mechanisms that generate the frequency, amplitude, duration and direction of propagation of uterine contractile activity. On the basis of current knowledge of the molecular control of uterine myocyte function, there are opportunities for systematic testing of the efficacy of a variety of available potential pharmacological agents and for the development of new agents. Taking advantage of these opportunities could result in an overall improvement in reproductive health.

INTRODUCTION

A non-invasive test, which could predict the presence of sperm during a testicular sperm extraction (TESE) procedure in men with non-obstructive azoospermia (NOA), would be of profound clinical importance. Inhibin B (Inh-B) and anti-Müllerian hormone (AMH) have been proposed as direct markers of Sertoli cell function and indirect markers of spermatogenesis.

METHODS

A search was conducted in the electronic databases MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through June 2009. Thirty-six different studies reported data on the predictive value of one or more index markers (serum Inh-B: 32 studies, seminal Inh-B: 5 studies, serum AMH: 2 studies, seminal AMH: 4 studies) and were included in the systematic review. Nine studies, which had serum Inh-B as index marker, met the predefined criteria and were included in the meta-analysis.

RESULTS

Serum Inh-B demonstrated a sensitivity of 0.65 (95% confidence interval [CI]: 0.56–0.74) and a specificity of 0.83 (CI: 0.64–0.93) for the prediction of the presence of sperm in TESE. When the pre-test probability of 41% was incorporated in a Fagan's nomogram, resulted in a positive post-test probability of 73% and a negative post-test probability of 23% for the presence of sperm in TESE.

CONCLUSIONS

Serum Inh-B cannot serve as a stand-alone marker of persistent spermatogenesis in men with NOA. Although limited, evidence on serum AMH and serum/seminal AMH do not support their diagnostic value in men with NOA.

BACKGROUND

Egg donation (ED) makes it possible for subfertile women to conceive. Pregnancies achieved using ED with unrelated donors are unique, since the entire fetal genome is allogeneic to the mother. The aims of this review were to evaluate the consequences of ED pregnancies and to place them in the special context of their atypical immunologic relationships.

METHODS

This review comprised an online search of English language publications listed in Pubmed/Medline, up to 29 January 2010. Seventy-nine papers met inclusion criteria. Using the literature and the authors' own experience, the relevant data on pregnancy outcome and complications, placental pathology and immunology were evaluated.

RESULTS

Multiple studies document that ED pregnancies are associated with a higher incidence of pregnancy-induced hypertension and placental pathology. The incidence of other perinatal complications, such as intrauterine growth restriction, prematurity and congenital malformations, is comparable to conventional IVF. During pregnancy, both local and systemic immunologic changes occur and in ED pregnancies these changes are more pronounced. There is almost no information in the literature on the long-term complications of ED pregnancies for the mother.

CONCLUSIONS

ED pregnancies have a higher risk of maternal morbidity. Owing to the high degree of antigenic dissimilarity, ED pregnancies represent an interesting model to study complex immunologic interactions, as the fully allogeneic fetus is not rejected but tolerated by the pregnant woman. Knowledge of the immune system in ED pregnancies has broader significance, as it may also give insight into immunologic aspects of tolerance in solid organ transplantation.

BACKGROUND

Mammalian oocytes are activated by intracellular calcium (Ca²⁺) oscillations following gamete fusion. Recent evidence implicates a sperm-specific phospholipase C zeta, PLC, which is introduced into the oocyte following membrane fusion, as the responsible factor. This review summarizes the current understanding of human oocyte activation failure and describes recent discoveries linking certain cases of male infertility with defects in PLC expression and activity. How these latest findings may influence future diagnosis and treatment options are also discussed.

METHODS

Systematic literature searches were performed using PubMed, ISI-Web of Knowledge and The Cochrane Library. We also scrutinized material from the United Nations and World Health Organization databases (UNWHO) and the Human Fertilization and Embryology Authority (HFEA).

RESULTS AND CONCLUSIONS

Although ICSI results in average fertilization rates of 70%, complete or virtually complete fertilization failure still occurs in 1–5% of ICSI cycles. While oocyte activation failure can, in some cases, be overcome by artificial oocyte activators such as calcium ionophores, a more physiological oocyte activation agent might release Ca²⁺ within the oocyte in a more efficient and controlled manner. As PLC is now widely considered to be the physiological agent responsible for activating mammalian oocytes, it represents both a novel diagnostic biomarker of oocyte activation capability and a possible mode of treatment for certain types of male infertility.

BACKGROUND

In this review, recent advances in the laboratory as well as embryological aspects of hCG priming in vitro maturation (IVM) cycles are described.

METHODS

This report is based on publications from literature searches and the authors' experience.

RESULTS

In IVM cycles, priming with hCG permits the recovery of a certain number of oocytes with an expanding/dispersed cumulus pattern which facilitates its identification within follicular fluid as compared with non-primed IVM cycles. The immature oocytes with dispersed cumulus cells (CC) at collection have high IVM rates and embryo development potentials. Moreover, a few in vivo matured oocytes with dispersed CC can be obtained, and these have produced good quality embryos. hCG can be given to patients when a dominant follicle reaches 10–12 mm to avoid negative effects on the sibling immature oocytes. ICSI should be performed at least 1 h after the first polar body extrusion. Embryo transfer time depends on quantity and quality of the embryos produced after IVM. Compared with slow freezing, vitrification is a more efficient method for freezing the embryos produced from IVM.

CONCLUSIONS

The data from the meta-analyses suggests that the effect on clinical outcome of gonadotrophin priming of IVM still needs to be studied. In order to improve the IVM programs, it is essential to define not only the clinical aspects but also the laboratory and embryological aspects.

BACKGROUND

Endometriosis is estimated to affect 1 in 10 women during the reproductive years. There is often delay in making the diagnosis, mainly due to the non-specific nature of the associated symptoms and the need to verify the disease surgically. A biomarker that is simple to measure could help clinicians to diagnose (or at least exclude) endometriosis; it might also allow the effects of treatment to be monitored. If effective, such a marker or panel of markers could prevent unnecessary diagnostic procedures and/or recognize treatment failure at an early stage.

METHODS

We used QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria to perform a systematic review of the literature over the last 25 years to assess critically the clinical value of all proposed biomarkers for endometriosis in serum, plasma and urine.

RESULTS

We identified over 100 putative biomarkers in publications that met the selection criteria. We were unable to identify a single biomarker or panel of biomarkers that have unequivocally been shown to be clinically useful.

CONCLUSIONS

Peripheral biomarkers show promise as diagnostic aids, but further research is necessary before they can be recommended in routine clinical care. Panels of markers may allow increased sensitivity and specificity of any diagnostic test.