Showing papers in "Human Fertility in 2000"

Long-term consequences of polycystic ovary syndrome: Results of a 31 year follow-up study

Abstract: A cohort of 786 women who received a diagnosis of polycystic ovary syndrome (PCOS) in the United Kingdom before 1979 was traced to investigate the long-term consequences of the syndrome. Data were obtained from death certificates for 70 women. Morbidity data were collected from general practice records and questionnaires for 319 women diagnosed with PCOS an average of 31 years previously and for 1060 age-matched control women. The proportion of women with involuntary infertility was 17.5% in the PCOS group compared with 1.3% in the control group. All-cause mortality in the cohort did not differ from that of the general population of women. Women with PCOS were not at significantly increased risk of mortality or morbidity from breast cancer but were at increased risk of endometrial cancer. Women with a history of PCOS had higher levels of several cardiovascular risk factors including diabetes, hypertension, raised plasma cholesterol and body mass index > 30 kg m(minus sign2). Mortality and morbidity from coronary heart disease did not differ significantly between the women with PCOS and comparison groups. Control of obesity is likely to be particularly important for women with a history of PCOS.

Large offspring syndrome and other consequences of ruminant embryo culture in vitro: Relevance to blastocyst culture in human ART

Abstract: In vitro production of embryos from domestic animals is used to augment conventional genetic improvement programmes in agriculture and to facilitate advances in gene transfer and cloning. However, production of embryos in vitro exposes them to hazards not normally encountered in vivo and, as a result, there have been unforeseen consequences including the large offspring syndrome. This syndrome is manifest as abnormal growth and development at fetal, neonatal and later stages after transfer of embryos cultured in vitro for up to 1 week after fertilization. Our embryo culture and fetal development studies have begun to characterize many of the genetic, metabolic and developmental features associated with the syndrome. This review considers the findings of these studies in the context of blastocyst production in vitro, emphasizing the impact of culture strategies on ruminant (cattle and sheep) embryo composition and developmental competence. The need to alter in vitro production strategies to safeguard oocytes and embryos during culture is discussed. Finally, the implications of experiences gained in domestic animal studies are considered in the context of current options for human embryo culture. The need for an appreciation of the sensitivity of the embryo to its environment and the possible short- and long-term consequences of inappropriate in vitro production strategies are considered.

Apoptosis in mammalian preimplantation embryos: regulation by survival factors.

Abstract: The formation of a developmentally competent mammalian blastocyst requires the transition from a unicellular state, the fertilized zygote, to a differentiated multicellular structure. In common with other developing organisms, generation of the required cell population involves the processes of cell division, differentiation and cell death, all of which can be regulated by peptide growth factors. Cell death in the preimplantation embryo occurs by apoptosis and, by analogy with other systems, may serve to eliminate unwanted cells during the critical developmental transitions that take place during this period. Cells may be eliminated because they are abnormal or possess defects, including damaged DNA or chromosomal abnormalities. At the early cleavage stages, apoptosis may be associated with activation of the embryonic genome and may contribute to the blastomere fragmentation commonly observed in human IVF embryos. The major wave of apoptosis occurs in a number of species in the inner cell mass of the blas...

In vitro fertilization: a long-term follow-up after treatment failure.

Abstract: There is a considerable body of psychological research on women presenting for in vitro fertilization (IVF), but relatively little on the long-term adjustment of such women after unsuccessful treatment. This study examined the adjustment (4--9 years after treatment) of a sample (n = 76) of women whose treatment had failed. At follow-up, it was found that eight (10.53%) of the women had conceived naturally and 16 (21.05%) had become adoptive parents. In comparison with population norms, the women who had not subsequently conceived or adopted (n = 52) were found to rate themselves as more highly stressed (P < 0.001), but rated themselves as higher in self-esteem (P < 0.001). However, when women who remained childless after unsuccessful IVF were compared with those who subsequently conceived or adopted, the former group rated themselves as more stressed (P < 0.05), more depressed (P < 0.001) and with a lower satisfaction with life (P < 0.005) and lower self-esteem (P < 0.05). Women who wished to adopt but were unable to do so made a major contribution to this negative pattern. The study indicates that infertility long after failed IVF treatment contributes to psychological dysfunction. It highlights the need to prepare women better for treatment failure and to ensure appropriate counselling is available when further IVF treatment is no longer appropriate.

Blastocyst culture: Toward single embryo transfers

Abstract: The routine culture and transfer of viable human blastocysts has been made possible by the development of sequential culture media, formulated to account for the changes in nutrient requirements of the embryo as it develops and differentiates. Resultant implantation rates of blastocysts transferred on day 5 are significantly higher than those obtained by the transfer of cleavage stage embryos transferred on day 2 or day 3 within the same programme. As a direct result of this increase in implantation rate, fewer blastocysts than cleavage stage embryos need to be transferred to obtain acceptable pregnancy rates, thereby reducing the incidence of multiple gestations. Blastocysts developed in sequential culture media are readily cryopreserved. The efficiency of in vitro fertilization (IVF) in a general patient population can be calculated using a model that takes into account the number of embryos transferred and cryopreserved, together with their respective implantation rates. Blastocyst transfer is associated with about a 20% increase in the efficiency of IVF compared with the transfer of cleavage stage embryos on day 3. The development of a suitable scoring system has enabled identification of those blastocysts with the highest developmental potential (70% implantation rate). The culmination of this work should be the move to the transfer of a single blastocyst for a significant number of patients.

Reproductive issues from the Islamic perspective

Abstract: The Islamic faith is regarded by its followers, Muslims, as a complete way of life. A multitude of nationalities practise Islam and also various sects, and as a result there are various interpretat...

Possible consequences of performing intracytoplasmic sperm injection (ICSI) with sperm possessing nuclear DNA damage.

Abstract: A number of studies have confirmed that sperm with damaged nuclear DNA are present in human ejaculate. It appears that these sperm are more likely to occur in men with low concentrations of sperm, or poor sperm motility or morphology. In assisted reproductive techniques, in particular intracyto-plasmic sperm injection (ICSI), there is a higher statistical chance that sperm possessing damaged DNA will be selected and used to fertilize oocytes. In light of this observation, the question of whether human sperm with damaged DNA can impair fertilization and embryo development is examined.

Pathogenesis of polycystic ovary syndrome: evidence for a genetically determined disorder of ovarian androgen production.

Abstract: Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in women of reproductive age. It is the major cause of anovulatory infertility and of hirsutism but its aetiology remains uncertain. The most consistent biochemical abnormality is hypersecretion of androgens. In this review, evidence is presented to support the view that a genetically determined abnormality of ovarian androgen secretion is the primary cause of the syndrome. Molecular genetic studies have demonstrated that CYP11a, the gene encoding P450 cholesterol side chain cleavage, is a major susceptibility locus for development of hyperandrogenism in PCOS.

The economic consequences of multiple gestation pregnancy in assisted conception cycles

Abstract: This study estimates the projected costs of multiple births resulting from assisted conception cycles (in vitro fertilization with or without intracytoplasmic sperm injection and ovarian stimulation with gonadotrophin). The estimates are modelled from the volume of services, treatment success and multiple gestation rates in recent registry data. The coverage is restricted to hospital costs associated with delivery and the trends are projected to 2000 in the United States. Sensitivity analyses tested different assumptions about per annum trends in effectiveness, multiple pregnancy rates and health costs. The national cost of in vitro fertilization cycles is US$470.2 million (£313.5 million) and the cost of the multiple pregnancies from in vitro fertilization is US$639.9 million (£426.7 million). The national cost of ovarian stimulation cycles is US$166.6 million (£111.1 million) and the cost of the multiple pregnancies from ovarian stimulation is US$257.3 million (£171.6 million). Although costs are a limited indicator of the burden of illness, the projected national cost of multiple pregnancy associated with assisted conception in 2000 is greater than the base cost of the treatment. Prevention of multiple pregnancy in assisted conception cycles should be a priority.

Obstetric outcome and follow-up of children born after in vitro fertilization (IVF).

Abstract: In vitro fertilization (IVF) is a well established and effective method for the treatment of infertility, but there is concern about the health of children born as a result of this procedure. The introduction of new technologies, such as intracytoplasmic sperm injection (ICSI), has increased concern that the offspring from such techniques may be at increased risk, particularly of malformations. Studies on obstetric and neonatal outcome and early infant development after IVF obtained from a Medline search were reviewed. Children born after IVF had a considerably higher risk of being born pre-term and with a lower birth weight than children conceived naturally. A high incidence of multiple births and maternal characteristics were the main factors responsible for the increase in adverse outcome. Novel strategies in assisted reproduction, including the development of single embryo transfer regimens and avoidance of multiple births, are required. There is also a need for further developmental follow-up of chil...

Nutritional and metabolic requirements of early cleavage stage embryos and blastocysts.

Abstract: During preimplantation human embryo development there is an increase in the synthesis of macromolecules and a demand for energy. Consequently, the metabolic requirements of the human embryo change as development proceeds from the zygote to the blastocyst stage. Evidence from a number of species indicates that before activation of the embryonic genome, human and other mammalian embryos have a preference for oxidizable energy substrates, particularly pyruvate, non-essential amino acids and glutamine. After embryonic genome activation, glucose and essential amino acids become increasingly important. As such, there is a switch in energy metabolism during preimplantation development from one based principally on aerobic respiration, to another based on oxidative metabolism and aerobic glycolysis.

Families from assisted conception: ethical and psychological issues.

Abstract: This article gives the findings of an in-depth study of the outcome for parents and children after assisted conception, namely in vitro fertilization and donor insemination. The study is of 54 families bringing up 110 children, 74 of whom were the result of these two medical interventions. The findings presented in this article deal specifically with the psychological issues and ethical dilemmas experienced by the parents of these two groups. Specific areas regarding in vitro fertilization are use of the term ‘test-tube baby’; religious and community attitudes to the use of assisted reproductive technology; and the effects of these attitudes on the families. The major issue of multiple births and their social outcomes is dealt with in the following article. The specific areas for donor insemination families are secrecy and reticence about the whole procedure; infertility as a continuing taboo subject; donor anonymity; and the resulting effect of donor anonymity on parenting children who do not have access...

The impact of the quality of family planning services on safe and effective contraceptive use: a systematic literature review.

Abstract: The aim of this review is to identify the features of family planning service provision that are influential in ensuring safe and appropriate contraceptive use and optimal effectiveness of user-dependent methods. A systematic search was carried out of the published and unpublished studies available up to December 1997 that examined the relationship between family planning service provision and contraceptive use. Articles that reported primary data on long-term outcomes were scored by at least two of the authors of the present study. Particular attention was paid to evaluating methods of measuring quality of care. A total of 142 articles were identified, but only 16 reported primary data relating to long-term outcomes. The quality of provider--client exchanges was found to have a net incremental effect on contraceptive use. Evidence of effectiveness of methods to improve uptake, continuation of method use, and safe and appropriate use of fertility control is scant. The evidence that is available indicates that training in communication with clients (particularly about side-effects of contraceptive methods) and an emphasis on client choice are key components of effective interventions. The tasks of listening to clients, and tailoring services to local needs, are crucial to the success of family planning service provision.

Blood flow changes in the ovarian and uterine arteries in women with normal and polycystic ovaries

Abstract: This review summarizes the haemodynamic changes in the ovarian and uterine arteries, as revealed by transvaginal colour Doppler ultrasonography, (i) in women with normal ovaries (group 1), (ii) in women with the polycystic ovary syndrome who ovulate in response to clomiphene citrate (group 2) and (iii) in women with polycystic ovaries who have a regular ovulatory menstrual cycle (group 3). In each group blood flow velocities in the intraovarian arteries increased during the menstrual cycle in the dominant ovary and remained high in the mid-luteal phase. There was no significant change in pulsatility index. In group 2, the longitudinal haemodynamic changes in the intraovarian arteries were similar to those seen in women with normal ovaries. However, the follicular and ovarian stromal blood flow velocities were greater in group 2 compared with the normal group. There was a significant increase in the pulsatility index of the uterine artery during the follicular phase of the menstrual cycle and a subsequent ...

Using prognostic models in clinical infertility.

Abstract: The chance that a couple who have tried to conceive for 12 months will succeed without assisted conception treatment is still higher than the chance that the same couple will benefit from treatment. In this context, it is important to assess the chance that a treatment-independent or ‘spontaneous’ pregnancy will occur in a couple whose wish for a child is unfulfilled. Prognostic models can be useful in this assessment. In recent years, prognostic models have been published both for the occurrence of ‘spontaneous’ pregnancy and for pregnancy after in vitro fertilization. This article discusses the theoretical aspects of prognostic modelling and assesses whether the current prognostic models are good enough to justify their use in clinical practice. The performance of existing models for the prediction of spontaneous conception was found to be acceptable on internal as well as on external validation. However, the performance of the existing models predicting IVF outcome was found to be disappointing on the ...

Ovulation induction for polycystic ovary syndrome.

Abstract: Polycystic ovary syndrome (PCOS) is the commonest cause of anovulatory infertility. Various factors influence ovarian function, and fertility is adversely affected by an individual being overweight or having high serum concentrations of LH. Strategies to induce ovulation include weight loss, oral anti-oestrogens (principally clomiphene citrate), parenteral gonadotrophin therapy and laparoscopic ovarian surgery. There have been no adequately powered randomized studies to determine which of these therapies provides the best overall chance of an ongoing pregnancy. Women with PCOS are at risk of ovarian hyperstimulation syndrome (OHSS) and so ovulation induction has to be monitored carefully with serial ultrasound scans. The recognition of an association between hyperinsulinaemia and PCOS has resulted in the use of insulin sensitizing agents, such as metformin, which appear to ameliorate the biochemical profile and improve reproductive function.

The role of inhibin in polycystic ovary syndrome.

Abstract: Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder which, in its severest manifestations, is associated with anovulation, hyperandrogenism and metabolic imbalance. The biochemical markers for the condition can include a significantly raised LH:FSH ratio and a raised testosterone concentration, indicating a derangement of the hypothalamo-pituitary-ovarian axis which may be primary or secondary to a primary ovarian pathology. The bioactive inhibins are heterodimeric glycoproteins consisting of α-βA (inhibin A) and α-βB (inhibin B) subunits. They play an endocrine role in co-regulating (with oestradiol) the suppression of FSH during the late follicular and luteal phases of the ovarian cycle and they are implicated in intraovarian paracrine signalling. Inhibin B, which is the predominant form in small pre-ovulatory follicles, increases in concentration from early in the follicular phase to reach a peak coincident with the onset of the decrease in FSH which forms the basis of the pattern of mo...

Euphoria or despair? Coping with multiple births from ART: what patients don't tell the clinics.

Abstract: Patients' perception of family life after a multiple birth: euphoria or Pandora's box? The aim of this article is to explore the realities of parenting children from a multiple pregnancy as an aid to decision-making about the number of embryos transferred. Outcome research regarding parenting of children from twin, triplet and higher order births is described and, in particular, children of multiple births from assisted reproductive technology. Current understanding of interpersonal relationships in multiple birth families is also discussed. The evidence from these various sources is put in the framework of social risk factors as an aid to predicting outcomes and as an essential part of decision-making with the full participation of patients. The implications of such an approach is presented in relation to support for such families. Case studies are included of three triplet families. Reference is made to fetal reduction as an option.

BFS recommendations for good practice on the storage of ovarian and prepubertal testicular tissue

Abstract: As technologies of potential clinical importance emerge, clinicians and scientists may be placed under pressure to practise them before they have undergone full evaluation. The storage of ovarian or testicular tissues are examples of technologies that could be considered by patients, or in the case of minors their parents, when desperate to retain fertility potential under threat by treatment for other diseases, particularly cancer therapies. A number of issues are raised by such requests and in considering good clinical practice, a background discussion about the storage of ovarian and testicular tissues is warranted. In this article, only the main background issues are given. More detailed discussions may be found in a number of recent publications (Nugent et al., 1997; Oktay et al., 1998a; Gosden et al., 1999).

Developing the clinical nurse specialist's role in fertility: do patients benefit?

Abstract: This article discusses the published studies surrounding the role of the clinical nurse specialist and its effect on patient care. Evidence is presented to indicate that the extended role of the clinical nurse specialist provides a positive benefit when centred on patient need. Fertility nurses have responded to the rapid developments within the field and demonstrated that they can deliver a high level of practice within assisted reproduction clinics. This article focuses on some of the areas of extended fertility nursing practice.

Function of the polycystic ovary.

Abstract: The mechanism of the increase in the number of follicles in polycystic ovaries (PCO) is still not understood, but most data indicate that folliculogenesis is abnormal at all stages. This increase is probably due to prolonged follicle growth in both ovulatory (ov) and anovulatory PCO (anovPCO) rather than over-recruitment from the primordial stage. There appear to be fewer follicles in ovPCO than in anovPCO and this may be due to slow growth combined with arrested development in the anovPCO, preventing the normal process of atresia. This idea is supported by data indicating that the preponderance of structures in anovPCO are functional follicles rather than atretic cysts. In contrast, follicles in ovPCO are primarily atretic, analogous to the situation in the normal ovary. Closer analysis of the function of these follicles reveals an intrinsic defect in the theca cell layer in the expression of the genes encoding steroidogenic enzymes. Although androgen production is increased in all PCOs, the serum concentrations of androgen tended to be higher in anovulatory women indicating that there may be a link between the ovarian concentration and anovulation. Granulosa cells in small follicles from anovPCO behave in a similar fashion to those in preovulatory follicles from normal ovaries in terms of steroidogenic responses. This, in combination with the finding of LH-responsiveness in small follicles from anovPCO, has led to the suggestion that these follicles are prematurely luteinized. The recent finding that follistatin gene regulation may be abnormal in women with polycystic ovary syndrome (PCOS) provides a new insight into the possible defect in the function of these ovaries. Elucidation of the precise nature of the defect may provide the key to understanding the apparent contradiction of increased steroidogenesis in the presence of abnormal and arrested follicle growth.

Hyperinsulinaemia and polycystic ovary syndrome

Abstract: Over the past 20 years, it has been established that hyperinsulinaemia is a fundamental disturbance in many women with polycystic ovary syndrome (PCOS). A subgroup of women with this syndrome have ‘metabolic PCOS’ which can be considered to be a pre-diabetic state. Clinically, this subgroup is most easily identified in obese women with a strong family history of diabetes in whom menstrual disturbance is the predominant feature. There is an urgent need to define the more subtle features in young lean women with PCOS, in whom the metabolic syndrome is yet to emerge, which would enable the prediction of future health risks. The molecular mechanisms of insulin resistance leading to hyper-insulinaemia are now being elucidated. Abnormalities of both insulin secretion and intracellular insulin signalling have both been proposed in women with PCOS. Strategies to lower serum insulin concentrations include diet, exercise and possibly, oral insulin sensitizing agents such as metformin. Although the short-term effica...

Polycystic ovary syndrome in adolescence and early adulthood.

Abstract: Polycystic ovaries and the associated syndrome are recognized as the most common cause of endocrine disturbances in adult women, but much less research has been performed to examine how polycystic ovary syndrome (PCOS) presents in girls and young women. Polycystic ovaries have been demonstrated in childhood, and there is evidence to show that even very young women may show symptoms and signs of the associated syndrome. Closer examination of younger populations (ˇ- 25 years of age), and in particular, studies of girls during the transition from puberty into early adulthood (adolescence), may provide new insights into the pathogenesis and natural history of polycystic ovaries and PCOS, and may indicate whether polycystic ovaries could potentially be considered as a marker for health screening. Consideration should be given to the management of girls and young women with polycystic ovaries and PCOS as this group may have different needs and health risks compared with older women.

BFS recommendations for good practice on the screening of egg and embryo donors

Abstract: Egg donation is the only method by which some women will be able to carry a healthy pregnancy. Such women include those who have premature ovarian failure, poor quality eggs or who carry a genetic disorder. Under these circumstances, egg donation is, and should remain, an acceptable treatment. However, it raises many legal, practical and ethical issues, one of which is the method by which donors are recruited and assessed. This article addresses the questions relating to the screening of donors and gives some background information relating to the ‘Recommendations for Good Practice’ agreed by the British Fertility Society. Some of the recommendations follow the same guidelines agreed for the screening of sperm donors (American Society for Reproductive Medicine, 1998; Barratt et al., 1998; British Andrology Society, 1999), although it is recognized that the differences between egg and sperm donors in terms of the availability and method of collection is such that it may not be appropriate for the same criteria to be applied in each case. In particular, the major shortage of egg donors means that many recipients will be denied treatment if the regulations are applied rigidly. The overwhelming guiding principle must be the interests of the child. Both donor and recipient couples are able to make an informed choice about whether treatment is provided. They are also interested in the child and it is imperative to give evidence to them to ensure that appropriate fully informed decisions are made. Unfortunately, egg donation is a relatively new technique and consequently some of the evidence that we would like to be able to give to patients is simply not available.

Pregnancy and miscarriage rates in 3978 donor insemination cycles: effect of age, parity and partner's infertility status on pregnancy outcome.

Abstract: The effects of age, parity and male infertility status on pregnancy outcome were studied in a cohort of 720 women receiving donor insemination (DI) treatment. Twenty-two percent of women failed to complete the treatment, leaving 562 women receiving 3202 cycles of DI for assessment. Of the 321 of pregnancies achieved, 57 (17.8%) ended in a mis-carriage. After further DI treatments, 64.7% of mothers who had miscarried succeeded in giving birth. There was some evidence to indicate a trend of decreasing pregnancy rate with increasing maternal age, although this result was not significant (log rank trend statistics = 3.44, P > 0.05). The pregnancy rates of multiparous and primiparous women were significantly different, irrespective of their partner's infertility status (azoospermia: log rank statistics = 3.74, P ˇ- 0.05; oligozoospermia: log rank statistics = 4.71, P < 0.03). Furthermore, multiparous women were more likely to become pregnant than primiparous women (azoospermia: hazard ratio = 1.29; oligozoospe...

Insulin sensitivity and fertility.

Abstract: This review sets in context significant recent advances in the understanding of the pathophysiology of polycystic ovary syndrome (PCOS). The occurrence of variable insulin sensitivity in individuals is discussed. Information is presented to demonstrate that prolonged anovulation decreases insulin sensitivity and, conversely, that improvement in insulin sensitivity normalizes ovarian function in PCOS. In addition, a meta-analysis of studies on metformin and troglitazone treatment in PCOS is presented.

Fertility nurses doing embryo transfers -- what is the impact of training?

Abstract: It has been demonstrated that embryo transfer during IVF treatment can be performed competently and successfully by nurses (Barber et al., 1996). The present study has examined the success of nurses in training using the standardized protocol of this Unit. Initially, three nurses (two experienced (training completed) and one inexperienced (training ongoing)) each performed 80 transfers, which were standardized to three embryos replaced per transfer. The study aimed to establish whether a standardized procedure was undertaken by the nurses and to assess the influence of one inexperienced nurse performing the procedure. A further study (study 2) was performed to assess the influence of three inexperienced nurses against three experienced nurses undertaking the same procedures. In study 1, the pregnancy rates were 27.5%, 38.8% and 40.0% and there was no significant difference in the clinical pregnancy rates. In study 2, the pregnancy rates were 18.7%, 20.0% and 20.0% for the inexperienced nurses, and 26.3%, ...

Intracytoplasmic sperm injection in assisted reproductive technology: an evaluation.

Abstract: Since the first reports of successful pregnancies in humans after treatment with intracytoplasmic sperm injection (ICSI), intensive investigations have focused on several important aspects of this form of assisted reproductive technology In addition to the technical development of ICSI and increasing understanding of the biochemical and biophysical processes involved during fertilization after injection of an immobilized sperm, studies have aimed to define the indications for patients for a first-line ICSI treatment One of the major concerns is of course the safety of the technique in terms of the health and reproductive life of the babies born after ICSI The rhesus monkey is an excellent model to investigate all aspects of this micromanipulation technique This article provides an evaluation of ICSI

Definition of polycystic ovary syndrome.

Abstract: This article aims to answer two questions in defining polycystic ovary syndrome (PCOS): what is PCOS and how should the syndrome be recognized in clinical practice? Whether PCOS is a primary or a secondary ovarian disease remains controversial. It has been suggested for many years that the main pathophysiological factor in PCOS is dysregulation of the relationship between the hypothalamus, the pituitary and the ovary. However, PCOS also involves intraovarian morphological and functional abnormalities. With respect to clinical practice, many reports have questioned the sensitivity as well as the specificity of a high LH concentration. Similarly, the biological hyperandrogenism of PCOS cannot define the syndrome. GnRH agonist or hCG tests are not convenient for the diagnosis of PCOS in practice. Stromal hyperplasia is considered to be indicative of PCOS but it is highly dependent on the settings of the ultrasound machine, thus use of the total ovarian area, the upper normal limit of which is 5.5 cm(2), is recommended. The need for diagnostic markers of PCOS depends on the clinical presentation. In the full-blown syndrome (classic PCOS), the clinical symptoms provide the most powerful indication and the association of the three components (hyperandrogenism, anovulatory dysfunction and metabolic abnormalities) has a strong diagnostic potency. In non-classic PCOS, a cost-effective and safe work-up should be applied, which includes ultrasonography and hormonal assays (basal serum concentrations of testosterone, sex hormone binding globulin, 17-hydroxyprogesterone, LH, FSH and prolactin). Asymptomatic PCOS may be discovered incidentally during ultrasonography, and it is important to take this finding into account when designing an ovulation induction protocol. In most cases of PCOS, the diagnosis may remain presumptive providing other diagnoses have been ruled out and the follow-up does not disclose any atypical development of the condition.