Embase Medline and PubMed databases, Google-indexed scientific literature and periodics from on-line University of Milan Bibliotecary Service were searched to identify relevant publications. In vivo human studies were mainly searched for, but when needed animal studies as well as in vitro and cell culture experiments were also considered.

Fertility, conception, implantation, fetal organogenesis and placentation are the critical stages potentially affected by nutrition during the periconceptional period. Reactive oxygen species (ROS) and total homocysteine (tHcy) plasma levels are factors involved in the respective mechanisms. The preconceptional period is particularly important since it affects both fertility and the early stages of gestation. Micronutrients' dietary intake and maternal status affect the different phases of the onset and development of pregnancy as well as of the conceptus.

Although human studies are scarce, and conclusive evidence is provided solely for periconceptional folate and prevention of neural tube defects (NTDs), the overall data indicate that micronutrients may affects fertility, embryogenesis and placentation, and the prophylactic use of some micronutrients may be useful in preventing several adverse pregnancy outcomes. Efforts to increase awareness of a healthy diet should be strengthened not only throughout pregnancy but also before. However, further researches in humans are necessary to optimise periconceptional micronutrient requirements.

We conducted a literature search and analyzed the published studies that reported methods for the assessment of hair growth. We review the basic physiology of hair growth, the development of methods for visually quantifying hair growth, the comparison of these methods with objective measurements of hair growth, how hirsutism may be defined using a visual scoring method, the influence of race and ethnicity on hirsutism, and the impact of hirsutism in diagnosing androgen excess and polycystic ovary syndrome.

Objective methods for the assessment of hair growth including photographic evaluations and microscopic measurements are available but these techniques have limitations for clinical use, including a significant degree of complexity and a high cost. Alternatively, methods for visually scoring or quantifying the amount of terminal body and facial hair growth have been in use since the early 1920s; these methods are semi-quantitative at best and subject to significant inter-observer variability. The most common visual method of scoring the extent of body and facial terminal hair growth in use today is based on a modification of the method originally described by Ferriman and Gallwey in 1961 (i.e. the mFG method).

Overall, the mFG scoring method is a useful visual instrument for assessing excess terminal hair growth, and the presence of hirsutism, in women.

A computerized literature search in MEDLINE, EMBASE, CENTRAL and randomized controlled trial (RCT) registries was performed independently by two reviewers, aiming to identify RCTs that evaluated the following research question: does GH addition increase the probability of pregnancy in poor responders undergoing ovarian stimulation with gonadotrophin releasing hormone (GnRH) analogues and gonadotrophins for IVF?

Six relevant RCTs were identified, including a total of 169 patients. GH addition significantly increased clinical pregnancy (rate difference: +16%, 95% CI: +4 to +28; fixed effects model) (number-needed-to-treat (NNT) = 6, 95% CI: 4–25) and live birth rates (rate difference: +17%, 95% CI: +5 to +30; fixed effects model) (NNT = 6; 95% CI: 3–20). Furthermore, GH addition was associated with a significantly higher proportion of patients reaching embryo transfer (rate difference: +22%, 95% CI: +7 to +36; fixed effects model).

The present meta-analysis provides evidence that GH addition increases the probability of clinical pregnancy and live birth in poor responders undergoing ovarian stimulation with GnRH analogues and gonadotrophins for IVF. However, the total number of patients analyzed is small and thus further RCTs are warranted to prove or disprove this finding.

Articles were obtained by searching PubMed until December 2008. A first search attempted to identify genes located on the X chromosome potentially important for spermatogenesis. A second part of the study was focused on those genes for which the role has already been studied in infertile patients.

Multiple genes located on the X chromosome are expressed in testicular tissues. The function of many genes, especially the cancer–testis genes, has not been studied so far. There were striking differences between mouse and human genes. In the second part of the study, the results of mutation analyses of seven genes (AR, SOX3, USP26, NXF2, TAF7L, FATE and AKAP4) are described. Except for AR, no infertility causing mutations have, thus far, been described. It cannot be excluded that some of the observed changes should be considered as risk factors for impaired spermatogenesis.

It can be concluded that, so far, the mutation analysis of X-linked genes in humans, presumed to be crucial for spermatogenesis or sperm quality, has been disappointing. Other approaches to learn more about male infertility are necessary.

Relevant studies were identified by searching Pubmed up to January 2009 with English language limitation. The following key words were used: (ovarian tissue or whole ovary) AND (transplantation) AND (cryopreservation or pregnancy). Using the literature and personal experience, we examined relevant data on the different exogenous and clinical factors affecting follicular development after grafting.

Clinical factors such as the patient's age and the transplantation sites influenced the lifespan of the graft. A heterotopic transplantation site is not optimal but offers some advantages and it may also promote the hormonal environment after a combined heterotopic and orthotopic transplantation. Exogenous factors such as antioxidants, growth factors or hormones were tested to improve follicular survival; however, their efficiency regarding further follicular development and fertility potential remains to be established.

Additional evidence is required to define optimal conditions for ovarian tissue transplantation. Alternatives such as whole ovary or isolated follicles transplantations require further investigation but are likely to be successful in humans in the future.

We conducted a systematic review of randomized clinical trials of hormone therapy (i.e. oral, transdermal, i.m.) and verbal memory, distinguishing studies in younger (i.e. ≤65 years of age; n = 9) versus older (i.e. >65 years; n = 7) women and studies involving estrogen alone versus estrogen plus progestogen. Out of 32 placebo-controlled trials, 17 were included (13 had no verbal memory measures and 2 involved cholinergic manipulations). We also provide a narrative review of 25 studies of executive function (two trials), since there are insufficient clinical trial data for systematic review.

There is some evidence for a beneficial effect of estrogen alone on verbal memory in younger naturally post-menopausal women and more consistent evidence from small-n studies of surgically post-menopausal women. There is stronger evidence of a detrimental effect of conjugated equine estrogen plus medroxyprogesterone acetate on verbal memory in younger and older post-menopausal women. Observational studies and pharmacological models of menopause provide initial evidence of improvements in executive function with hormone therapy.

Future studies should include measures of executive function and should address pressing clinical questions; including what formulation of combination hormone therapy is cognitively neutral/beneficial, yet effective in treating hot flashes in the early post-menopause.

MEDLINE searches were done by topic (epidemiology, age and reproduction, sexual function, delayed childbearing and specific contraceptive methods). The topic summaries were presented to the Workshop Group and omissions or disagreements were resolved by discussion.

The decline in fecundity in the fifth decade is insufficient for contraceptive purposes. Thus a family planning method is needed. Sterilization is by far the most common method in several countries. Copper intrauterine devices and hormone intrauterine systems have similar effectiveness, with fewer than 1% failures in the first year of typical use. Special considerations in this age group include the frequency of menstrual irregularity, sexual problems and the possibility of menopausal symptoms, all of which may respond to hormonal methods of contraception.

Women should be advised to continue with a contraceptive method until they have reached the menopause with its natural state of sterility.

A review of monochorionic (MC) monozygotic (MZ) placentation in the pathogenesis of congenital anomalies and CP was conducted using the PubMed, MEDLINE, EMBASE and Cochrane databases.

Zygote division and MC placentation have serious implications for the development of both conceptuses. Most reports observe predominantly cerebral abnormalities in one or both conceptuses. These cerebral abnormalities often present as CP or other disabilities attributable to central nervous system impairment. In addition to the anomalies in central nervous system development, anomalies in the fetal development of a wide variety of other organs have been reported with MC MZ twinning.

CP and congenital anomalies share a common pathogenic mechanism attributable to MZ twinning. These abnormalities in singletons are coincident with very early loss of one conceptus. The quantitative contribution of monozygosity and monochorionicity to the genesis of CP and congenital anomalies needs to be made.

A bibliographic search of English language publications of four computerized databases was undertaken with no time restriction set for publications.

A total of 64 studies met the inclusion criteria and were included in the review. The research syntheses revealed there were distinct differences between patient and non-patient (known, commercial, volunteer and potential) donors on demographic characteristics, motives for donation, and issues relating to disclosure and attitudes towards the resultant offspring. Further, studies have found that a significant proportion of oocyte donors and women from the general population were prepared to donate their oocytes as identifiable donors. Studies which have examined the experiences of donors report positive experiences of oocyte donation. However, a number of methodological limitations relating to the oocyte donation research literature have been identified in this systematic review.

Differences between donor groups on a range of factors highlight the need for tailored psychosocial evaluation and counselling. The review has demonstrated that it is not useful to generalize across donor groups on various factors relating to oocyte donation.

We systematically searched the literature for papers reporting prediction models in reproductive medicine for three strategies: expectant management, intrauterine insemination (IUI) or in vitro fertilization (IVF). We evaluated which phases of development these models had passed, distinguishing between (i) model derivation, (ii) internal and/or external validation, and (iii) impact analysis. We summarized their performance at external validation in terms of discrimination and calibration.

We identified 36 papers reporting on 29 prediction models. There were 9 models for the prediction of treatment-independent pregnancy, 3 for the prediction of pregnancy after IUI and 17 for the prediction of pregnancy after IVF. All of the models had completed the phase of model derivation. For six models, the validity of the model was assessed only in the population in which it was developed (internal validation). For eight models, the validity was assessed in populations other than the one in which the model was developed (external validation), and only three of these showed good performance. One model had reached the phase of impact analysis.

Currently, there are three models with good predictive performance. These models can be used reliably as a guide for making decisions about fertility treatment, in patients similar to the development population. The effects of using these models in patient care have to be further investigated.

Articles were identified in PubMed, Embase and PsycLIT as well as manually retrieved from literature citations for the time period from 1999 to 2008. Inclusion criteria were (i) qualitative or quantitative design, (ii) focus on patients previous to or during their reproductive lifespan and (iii) dealing with aspects such as (1) impact of fertility issues in cancer patients or (2) health professionals' and/or patients' attitudes towards fertility preservation or (3) counselling.

Twenty-four studies were identified. According to the studies on aspect (1), fertility is an important issue for cancer patients. Health professionals as well as patients and parents consider fertility preservation as an important option for young cancer patients; all parties involved, however, were noted to have knowledge and information deficits. Patients recalling counselling about the impact of cancer treatment on fertility ranged from 34% to 72%. Counselling is far from being offered globally to all patients at risk, and providing information seems to be selective.

The existing literature demonstrates the need for and the limits of current counselling. Future research should target the means to facilitate the decision-making process for patients and health professionals.

We review changes associated with decreased fertilization rates and developmental potential of aged oocytes, and we present methods and approaches that prevent or delay oocyte aging.

Cellular and molecular abnormalities occur during oocyte aging, but prevention, delay or reversal is possible to various extents. Modifying existing culture conditions, or treatment of oocytes with agents such as caffeine, DL-dithiothreitol, nitric oxide or trichostatin A may correct molecular pathways that are affected by aging, and thus benefit and improve success rates in modern ART.

Aging of oocytes is characterized by a sequence of molecular processes that deteriorate during aging and negatively impact fertilization and development. However, oocyte aging can be delayed or reversed by various treatments to increase success rates and produce increased numbers of healthy embryos, preventing failures or abnormalities that are frequently associated with ART using aged oocytes.

In order to quantify the association between OC use and colorectal cancer risk, we performed a systematic review and meta-analysis of studies on this issue. We identified all relevant studies published, in English, as original articles up to December 2008 through a search of the literature using PubMed and EMBASE, and by reviewing the references from the retrieved articles.

The summary relative risk of colorectal cancer for ever versus never OC use was 0.82 (95% confidence interval, CI, 0.69–0.97) from 11 case–control studies, 0.81 (95% CI, 0.75–0.89) from seven cohort studies, and 0.81 (95% CI, 0.72–0.92) from all studies combined. The results were similar for colon and rectal cancer. No difference was evident according to duration of OC use both for colon and rectal cancer, although there is an indication that the protection is stronger for more recent use (OR = 0.70, 95% CI, 0.53–0.90, on the basis of four studies).

Epidemiological data consistently indicate that OC users have a reduced risk of colorectal cancer, and that the protection is greater for recent use in the absence, however, of a duration–risk relation.

The scientific literature was searched for studies reporting on the several aspects of mitochondrial activity in mammalian testis, sperm, oocytes, early embryos and embryonic stem cells.

ATP synthesis and ROS production are the most discussed aspects of mitochondrial function. Metabolic shifts from mitochondria-produced ATP to glycolysis occur at several stages, notably during gametogenesis and early embryo development, either reflecting developmental switches or substrate availability. The exact role of sperm mitochondria is especially controversial. Mitochondria-generated ROS function in signalling but are mostly described when produced under pathological conditions. Mitochondria-based calcium signalling is primarily important in embryo activation and embryonic stem cell differentiation. Besides pathologically triggered apoptosis, mitochondria participate in apoptotic events related to the regulation of spermatogonial cell number, as well as gamete, embryo and embryonic stem cell quality. Interestingly, data from knock-out (KO) mice is not always straightforward in terms of expected phenotypes. Finally, recent data suggests that mitochondrial activity can modulate embryonic stem cell pluripotency as well as differentiation into distinct cellular fates.

Mitochondria-based events regulate different aspects of reproductive function, but these are not uniform throughout the several systems reviewed. Low mitochondrial activity seems a feature of ‘stemness’, being described in spermatogonia, early embryo, inner cell mass cells and embryonic stem cells.

A systematic review was undertaken of the published literature on Treg cells in the ovary, testes, uterus and gestational tissues in pregnancy, and their link with infertility, miscarriage and pathologies of pregnancy. An overview of current knowledge on the generation, activation and modes of action of Treg cells in controlling immune responses is provided, and strategies for manipulating regulatory T-cells for potential applications in reproductive medicine are discussed.

Studies in mouse models show that Treg cells are essential for maternal tolerance of the conceptus, and that expansion of the Treg cell pool through antigen-specific and antigen non-specific pathways allows their suppressive actions to be exerted in the critical peri-implantation phase of pregnancy. In women, Treg cells accumulate in the decidua and are elevated in maternal blood from early in the first trimester. Inadequate numbers of Treg cells or their functional deficiency are linked with infertility, miscarriage and pre-eclampsia.

The potency and wide-ranging involvement of Treg cells in immune homeostasis and disease pathology indicates the considerable potential of these cells as therapeutic agents, raising the prospect of their utility in novel treatments for reproductive pathologies.