Category Archives: Human Reproduction

BACKGROUND

Understanding the aetiology of subfertility and female reproductive tract disorders at a molecular level may improve success rates in fertility treatment. Such understanding may be gained by the application of metabonomics technologies to tissues or biofluids. Metabonomics is concerned with the quantification of molecules in the metabolome and uses nuclear magnetic resonance (NMR) spectroscopy as one of the main technological platforms. This review concentrates on NMR studies of the female reproductive tract and discusses further possible applications. While full metabolic profiling is relatively recent, targeted NMR studies of biofluid and tissue has a longer history.

METHODS

Searches were carried out on MEDLINE^®, PubMed, SciFinder^® Scholar 2007 and ISI Web of Knowledge^SM for papers about NMR spectroscopy or metabonomics of the female reproductive tract and subfertility.

RESULTS

NMR spectroscopy has been employed for the compositional analysis of various elements of the female reproductive tract, including cervical mucus, follicular fluid (FF), ovarian tissue, fallopian tubes and uterine matter. NMR was used to document for the first time a change in FF lipoprotein concentration during follicular development. NMR analysis of granulosa cells from rats has revealed that follicle-stimulating hormone increases the activity of the pentose pathway, having crucial implications for ovarian stimulation regimens. In the uterine matter work, it has been shown by NMR that glycolysis is rapidly stimulated by estrogen, and in another study, citrate in uterine fluid was found as a potential biomarker for adenomyosis. NMR has also been used to show that chlamydiae are able to achieve higher energy reserves by stimulating glucose transport in host cells.

CONCLUSIONS

A range of NMR spectroscopic techniques have been applied to the analysis of the female reproductive tract, however great potential remains for further studies. Incorporation of metabonomics techniques into female fertility research may be valuable for understanding subfertility and predicting outcomes of assisted conception treatments.

BACKGROUND

The impact of gr/gr deletions on male fertility is unclear. These partial deletions of the AZFc region of the Y chromosome have been detected more frequently in infertile patients. However, few individual studies have demonstrated a statistically significant association. This study aims to quantify the strength of association between gr/gr deletions and male infertility, and to explore potential sources of heterogeneity, including ethnicity and geographical location.

METHODS

Medline was searched up to 31 December 2009 for full articles investigating the prevalence of gr/gr deletions in infertile and control men. A pooled odds ratio (OR) was estimated by a random-effects model. Heterogeneity was assessed by the Cochran's Q test, and quantified by I² statistic.

RESULTS

A total of 18 case–control studies, including 6388 cases and 6011 controls, met our inclusion criteria and showed that gr/gr deletions were present in 6.86% of cases and 4.69% of controls. The association between gr/gr deletions and infertility was significant (P < 0.001), with a pooled random-effects OR of 1.76 (1.21–2.66) for infertile men versus normozoospermic controls (13 studies). The test for heterogeneity among studies yielded a Q test P = 0.089 with I² value of 37%, indicating moderate heterogeneity. The association between gr/gr deletions and infertility was dependent on ethnicity and geographic region.

CONCLUSIONS

Our meta-analysis comprising >12 000 men demonstrates that gr/gr deletions occur more frequently in infertile than control men. The association between gr/gr deletions and infertility varies according to ethnicity and geographic region, with an association reaching significance among Caucasian men, in Europe and the Western Pacific region.

BACKGROUND

The optimal ovarian stimulation dose to obtain the best balance between the probability of pregnancy and the risk of complications, while maximizing cost-effectiveness of in vitro fertilization (IVF) treatment, is yet to be established.

METHODS

A systematic search of the electronic databases PubMed, EMBASE and Cochrane library, from 1984 until October 2009 for randomized controlled trials comparing different doses of recombinant FSH in IVF, was performed.

RESULTS

Ten studies (totaling 1952 IVF cycles) were included in the present meta-analysis, comprising patients younger than 39 years with regular menstrual cycle, normal basal FSH levels and two normal ovaries. Comparison was made between studies using a daily dose of 100 versus 200 IU recFSH, and between 150 versus 200 IU recFSH or higher. Although oocyte yield was greater in the >200 IU/day dose group, pregnancy rates were similar compared with lower dose groups. The risk of insufficient response to ovarian stimulation was greatest in the 100 IU/day dose group. The risk of developing ovarian hyperstimulation syndrome was greater in the >200 IU/day dose group. The number of embryos available for cryopreservation was lowest in the 100 IU/day group, but similar comparing the 150 IU/day and the >200 IU/day dose groups.

CONCLUSIONS

This meta-analysis suggests that the optimal daily recFSH stimulation dose is 150 IU/day in presumed normal responders younger than 39 years undergoing IVF. Compared with higher doses, this dose is associated with a slightly lower oocyte yield, but similar pregnancy and embryo cryopreservation rates. Furthermore, the wide spread adherence to this optimal dose will allow for a considerable reduction in IVF costs and complications.

BACKGROUND

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting 8–12% of women. Lifestyle modification, including increased physical activity, is the first-line approach in managing PCOS. A systematic review was performed to identify and describe the effect of exercise as an independent intervention on clinical outcomes in PCOS.

METHODS

Five databases were searched with no time limit. A pre-specified definition of PCOS was not used. Studies were included if exercise therapy (aerobic and/or resistance) could be evaluated as an independent treatment against a comparison group. Outcomes measured included cardiovascular risk factors [insulin resistance (IR), lipid profiles, blood pressure and weight] and reproductive measures (ovulation, menstrual regularity and fertility outcomes). Quality analysis was performed based on the Cochrane Handbook of Systematic Reviews and the Quality of Reporting of Meta-Analyses checklist.

RESULTS

Eight manuscripts were identified (five randomized controlled trials and three cohort studies). All studies involved moderate intensity physical activity and most were of either 12 or 24 weeks duration with frequency and duration of exercise sessions ranging between studies. The most consistent improvements included improved ovulation, reduced IR (9–30%) and weight loss (4.5–10%). Improvements were not dependant on the type of exercise, frequency or length of exercise sessions.

CONCLUSIONS

Exercise-specific interventions in PCOS are limited. Studies vary considerably in design, intensity and outcome measures; therefore conclusive results remain elusive. Larger, optimally designed studies are needed to both gain insights into the mechanisms of exercise action and to evaluate the public health impact of exercise of PCOS.

BACKGROUND

Combined oral contraceptives (OCs) inhibit ovulation, substantially reduce the volume of menstrual flow and may hypothetically interfere with implantation of refluxed endometrial cells. The aim of this review is to establish if OC use influences the risk of endometriosis.

METHODS

We performed a MEDLINE search to identify all studies published in the last four decades (January 1970 to January 2010) in the English language on the relationship between OC exposure and risk of endometriosis. Two authors abstracted data on standardized forms.

RESULTS

We identified 608 potentially relevant studies and 18 studies (6 cross-sectional, 7 case–control and 5 cohort) were selected. Pooling of the results derived from all the included reports independently from study design, yielded a common relative risk of 0.63 [95% confidence interval (CI), 0.47–0.85] for current OC users, 1.21 (95% CI, 0.94–1.56) for past users and 1.19 (95% CI, 0.89–1.60) for ever users. Methodological drawbacks, such as uncertain temporal relationship between exposure and outcome in cross-sectional studies and suboptimal selection of controls in case–control studies, limit the quality of the available evidence.

CONCLUSIONS

The risk of endometriosis appears reduced during OC use. However, it is not possible to exclude the possibility that the apparent protective effect of OC against endometriosis is the result of postponement of surgical evaluation due to temporary suppression of pain symptoms. Confounding by selection and indication biases may explain the trend towards an increase in risk of endometriosis observed after discontinuation, but further clarification is needed. To date, the hypothesis of recommending OCs for primary prevention of endometriosis does not seem sufficiently substantiated.

BACKGROUND

There are many types of ovarian activity that occur in women. This review provides information on the relationship between the hormone values and the degree of biological response to the hormones including the frequency and degree of uterine bleeding. The continuous process is termed the ‘Continuum’ and is thus similar to other processes in the body.

METHODS

This review draws on information already published from monitoring ovarian activity by urinary oestrogen and pregnanediol measurements using timed 24-h specimens of urine. Much of the rationalization was derived from 5 to 6 year studies of girls progressing from childhood to adulthood, women progressing through menopause, and the return of fertility post-partum. During these times, all the reported types of ovarian activity were encountered.

RESULTS

All cycle types can be understood in terms of steps in the normal maturation of fertility at the beginning of reproductive life, its return post-partum and its demise at menopause. Each step merges into the next and therefore the sequence is termed the ‘Continuum’. Unpredictable movement from fertile to infertile types and back can occur at any time during reproductive life. Stress is a major causative factor. Hormonal definitions for each step, the relevance of the various cycle types in determining fertility and in the initiation of uterine bleeding and the roles of the pituitary hormones in causing them, are presented.

CONCLUSIONS

The findings explain the erratic fertility of women and why ovulation is not always associated with fertility. They provide an understanding of the various types of ovarian activity and their relation to pituitary function, fertility and uterine bleeding.