Ovulation induction in perspective

It has been suggested recently that, in some quarters, IVF be offered as first-line therapy to all infertile couples, regardless of the type of infertility. Hence, the time was thought right to scrutinise the results and complications of ovulation induction for anovulatory infertile couples. In addition to examining the outcome of conventional treatment with gonadotrophins and clomiphene citrate, special attention has been paid to the suggested improvement of results by taking into account the influence of obesity and the use of a low-dose gonadotrophin protocol. The possible contribution of more recent additions to the armamentarium such as insulin sensitizers and aromatase inhibitors, although still at an infant stage, are promising. Attention has been given to the prevention and treatment of ovarian hyperstimulation syndrome. The use of intra-uterine insemination (IUI) as an adjuvant to induction of ovulation and controlled ovarian hyperstimulation (COH) is examined. The very firm conclusion has been reached that, taking into account efficiency, complication rate and cost of treatment, at this stage, women with hypogonadotrophic hypogonadism or polycystic ovary syndrome should be offered accepted methods of ovulation induction and that couples with 'unexplained' or 'multifactorial subfertility' should still be exposed to COH with IUI and only after the failure of these therapies, be offered IVF.     

Androgens and the ageing male

Hypogonadal men share a variety of signs and symptoms such as decreased muscle mass, osteopoenia, increased fat mass, fatigue, decreased libido and cognitive dysfunctions. Controlled trials have demonstrated favourable effects of androgen substitution therapy on these signs and symptoms in men with severe primary or secondary hypogonadism. Thus, androgen substitution therapy is warranted in men with true hypogonadism at all ages. Symptoms experienced by otherwise healthy ageing males are non-specific and vague, although some may be similar to symptoms of hypogonadism. Therefore, the term 'andropause' has been suggested. However, testosterone levels show no or only modest variation with age in men; with large prospective studies suggesting a maximal decline of total testosterone of 1.6% per year. Thus, in contrast to the sudden arrest of gonadal activity in females around menopause, men do not have an andropause. As large placebo-controlled studies of androgen treatment in elderly males are lacking, proper risk assessment of adverse effects such as prostate cancer following testosterone treatment in elderly males is completely lacking. In the future, testosterone therapy may prove beneficial in some elderly males with low-normal testosterone levels. However, at this point in time, widespread use of testosterone in an elderly male population outside controlled clinical trials seems inappropriate.     

Varicocele treatment in the light of evidence-based andrology

Treatment of varicoceles became the most common treatment for male infertility merely on an empirical basis. However, in the age of evidence-based medicine it is surprising that only a few, and mainly recent, randomized controlled clinical trials with relevant outcome parameters have been published to allow adequate judgement of treatment effectiveness. Moreover, difficulties in study design could also be detected in most of these high-quality studies. Despite these difficulties and in contrast to the majority of uncontrolled studies on varicocelectomy, meta-analysis of these randomized controlled clinical studies involving 385 patients showed no significant treatment benefit and questions the common practice of varicocelectomy. Even the high-quality studies show conflicting results and therefore the topic of varicocele treatment will remain controversial and further randomized clinical trials should readdress this issue. For the time being, intervention by surgical or angiographic occlusion of the spermatic vein cannot be recommended.     

Clinical management of low ovarian response to stimulation for IVF: a systematic review

Poor response is not a rare occurrence in ovarian stimulation. Although not fully accepted, the most dominant criteria for poor ovarian response are small numbers of follicles developed or oocytes retrieved, and low estradiol (E2) levels after the use of a standard stimulation protocol. There is no ideal predictive test as the poor responder is revealed only during ovulation induction; however, increased levels of day 3 FSH and E2 as well as decreased levels of inhibin B can be used to assess ovarian reserve. Several protocols have been proposed for clinical management of low ovarian response in IVF. Although high doses of gonadotrophins have been used by the vast majority of authors, results have been controversial and prospective randomized studies have shown little or no benefit. The few available relevant studies do not indicate that recombinant FSH improves outcome. Flare-up GnRH agonist protocols (including all dosage varieties) produce better results than standard long luteal protocols. Luteal initiation GnRH agonist 'stop' protocols were shown to improve ovarian response according to prospective studies with historical controls, but this was not confirmed by well-designed prospective, randomized, controlled studies. The few available data obtained with GnRH antagonists have not shown any benefits. Adjuvant therapy with growth hormone (GH) or GH-releasing factors results in no significant improvement. The use of corticosteroids reduces the incidence of poor ovarian response in women undergoing IVF treatment. The limited data obtained with nitric oxide donors are encouraging. Pretreatment with combined oral contraceptives prior to stimulation may help ovarian response. No benefit was observed with standard use of ICSI or assisted hatching of zona pellucida. Finally, natural cycle IVF has produced results which are comparable with those obtained with stimulated cycles in true poor responders. Well-designed, large-scale, randomized, controlled trials are needed to assess the efficacy of these different management strategies.     

Hormones and cardiovascular health in women

Cardiovascular diseases (CVDs) may have their origin beforebirth: the combination of being small at birth and having anoverly rich post-natal diet increases the likelihood of obesityand of acquiring a specific metabolic syndrome in adulthoodthat carries an increased risk of CVD. The incidence of CVDand mortality is very low in women of reproductive age but risesto a significant level in older women. In this article, we discussCVD in relation to hormonal contraception, pregnancy and polycysticovarian syndrome (PCOS) in younger women and menopause in olderwomen. Women with PCOS have a higher risk of diabetes and hypertension,but studies to date have not shown an effect on CVD events.Use of combined hormonal contraception has only small effectson CVD because of the low baseline incidence of myocardial infarction(MI), stroke and venous thromboembolism (VTE) among young women.Women with existing risk factors or existing CVD, however, shouldconsider alternative contraception. In pregnancy, CVD is rare,although, in the West, it now accounts for a significant proportionof maternal mortality as the frequency of obstetrical causesof mortality has substantially declined. The frequency of VTEis 15 per 10 000 during pregnancy and the post-partum period.In older women, menopause causes a slightly higher risk of MIafter allowing for age, although there is substantial heterogeneityin the results of studies on menopause and age at menopauseand MI. A larger effect might have been expected, because estrogenreduces the risk of developing atherosclerosis in premenopausalwomen, whereas in post-menopausal women who may have establishedatherosclerotic disease, estrogen increases the risk of myocardialdisease through the effects on plaque stability and clot formation.Recent trial results indicate that hormone treatment in menopausedoes not favourably affect the risk of MI, stroke or other vasculardisease. Thus, prevention of CVD should rely on diet and fitness,low-dose aspirin and treatment of hypertension, hyperglycaemiaand hyperlipidaemia.     

Women's emotional adjustment to IVF: a systematic review of 25 years of research

This review provides an overview of how women adjust emotionally to the various phases of IVF treatment in terms of anxiety, depression or general distress before, during and after different treatment cycles. A systematic scrutiny of the literature yielded 706 articles that paid attention to emotional aspects of IVF treatment of which 27 investigated the women's emotional adjustment with standardized measures in relation to norm or control groups. Most studies involved concurrent comparisons between women in different treatment phases and different types of control groups. The findings indicated that women starting IVF were only slightly different emotionally from the norm groups. Unsuccessful treatment raised the women's levels of negative emotions, which continued after consecutive unsuccessful cycles. In general, most women proved to adjust well to unsuccessful IVF, although a considerable group showed subclinical emotional problems. When IVF resulted in pregnancy, the negative emotions disappeared, indicating that treatment-induced stress is considerably related to threats of failure. The concurrent research reviewed, should now be underpinned by longitudinal studies to provide more information about women's long-term emotional adjustment to unsuccessful IVF and about indicators of risk factors for problematic emotional adjustment after unsuccessful treatment, to foster focused psychological support for women at risk.     

DHEA therapy for women: effect on sexual function and wellbeing

DHEA is increasingly available commercially as a supplement aimed at improving libido and wellbeing in postmenopausal women. However there is scant evidence to support the use of DHEA for this purpose, and safety data for DHEA therapy are lacking. Dehydroepiandrosterone (DHEA) and its sulphate DHEAS are the most abundant circulating sex steroid hormones in women, providing a large precursor reservoir for the intracellular production of androgens and oestrogens in non-reproductive tissues. Levels of DHEA and DHEAS decline with age. It has been proposed that restoring the circulating levels of these steroids to those found in young people may have anti-ageing effects and improve wellbeing and sexual function. However this is not supported by the published literature. We have reviewed the physiology of DHEA and DHEAS in women and the published literature pertaining to the use of DHEA therapy for libido and wellbeing in postmenopausal women. The literature was searched using Medline (Ovid) and Pub-Med for original studies. Overall, the interpretation of data from randomised controlled trials conducted in well women is limited by inadequate sample size and short treatment durations with inconsistent results for the outcomes of libido and wellbeing. Studies of DHEA in women with adrenal insufficiency, although indicating potential improvements in mood and libido, are also limited by their short treatment phase durations. In addition safety data for DHEA therapy are lacking. The potential value of DHEA therapy for women still requires exploration in adequately powered well-designed randomised placebo-controlled trials. The studies of DHEA therapy in women with adrenal insufficiency suggest that this group is the most likely to derive health benefits from DHEA supplementation.     

Intrauterine insemination: a systematic review on determinants of success

Intrauterine insemination (IUI) is a frequently indicated therapeutic modality in infertility. Here, a systematic review of the literature was performed to examine the current status of clinical and laboratory methodologies used in IUI and the impact of female and male factors on pregnancy success. Emphasis was centred in questioning the following: (i) the value of IUI against timed intercourse; (ii) IUI application with or without controlled ovarian hyperstimulation; (iii) timing and frequency of IUI; and (iv) impact of various parameters (male/female) on the prediction of pregnancy outcome. The odds of multiple pregnancy occurrence and its risk factors, as well as the cost-effectiveness of IUI treatment compared with more complex assisted reproductive technologies are discussed. A computerized literature search was performed including Medline and the Cochrane library, as well as a crossover search from retrieved papers. It is concluded that although IUI is a successful contemporary treatment for appropriately selected cases of female and/or male infertility, further research is needed through well-designed studies to improve the methodologies currently utilized. Importantly, the clinical management of the infertile couple should be performed in an expedited manner taking into consideration the age of the woman, the presence of multifactorial infertility and cost-effectiveness of the available treatment alternatives.     

The varicocele dilemma

There is probably no subject that is more controversial in the area of male infertility than varicocele. The overwhelming majority of non-urologist infertility specialists in the world are extremely sceptical of the role of varicocele or varicocelectomy in the treatment of male infertility. Directors of most assisted reproductive technologies (ART) programmes view the enthusiasm with which urologists approach varicocelectomy as a potential impediment to the couple that is getting older and do not have much time left to become pregnant using ART. There are many credible, well-controlled studies which show no effect of varicocelectomy on fertility. There are also a few 'controlled' studies that favour varicocelectomy, but all can be criticised on the basis of patient selection bias. Thus the great weight of evidence from controlled studies is against varicocelectomy and the reports supporting varicocelectomy are extremely weak. Finally, the reports that semen parameters are improved by varicocelectomy is flawed by uncontrolled observations and the failure to take into account the variability of semen analysis in infertile men and its regression toward the mean. Many control studies have demonstrated that, because of this variability, men with an initially low sperm count tend later to have higher sperm counts in the absence of any treatment whatsoever.     

Breast cancer risk with postmenopausal hormonal treatment

This review was designed to determine from the best evidence whether there is an association between postmenopausal hormonal treatment and breast cancer risk. Also, if there is an association, does it vary according to duration and cessation of use, type of regimen, type of hormonal product or route of administration; whether there is a differential effect on risk of lobular and ductal cancer; and whether hormone treatment is associated with breast cancers that have better prognostic factors? Data sources for the review included Medline, the Cochrane Database of Systematic Reviews (Cochrane Library, 2005) and reference lists in the identified citations. Eligible citations addressed invasive breast cancer risk among postmenopausal women and involved use of the estrogen products with or without progestin that are used as treatment for menopausal symptoms. Abstracted data were demographic groupings, categories of hormone use, categories of breast cancer, two-by-two tables of exposure and outcome and adjusted odds ratios, relative risks (RRs) or hazard rates. Average estimates of risk were weighted by the inverse variance method, or if heterogeneous, using a random effects model. The average risk of invasive breast cancer with estrogen use was 0.79 [95% confidence interval (95% CI) = 0.61-1.02] in four randomized trials involving 12 643 women. The average breast cancer risk with estrogen-progestin use was 1.24 (95% CI = 1.03-1.50) in four randomized trials involving 19 756 women. The average risks reported in recent epidemiological studies were higher: 1.18 (95% CI = 1.01-1.38) with current use of estrogen alone and 1.70 (95% CI = 1.36-2.17) with current use of estrogen-progestin. The association of breast cancer with current use was stronger than the association with ever use, which includes past use. For past use, the increased breast cancer risk diminished soon after discontinuing hormones and normalized within 5 years. Reasonably adequate data do not show that breast cancer risk varies significantly with different types of estrogen or progestin preparations, lower dosages or different routes of administration, although there is a small difference between sequential and continuous progestin regimens. Epidemiological studies indicate that estrogen-progestin use increases risk of lobular more than ductal breast cancer, but the number of studies and cases of lobular cancer remains limited. Among important prognostic factors, the stage and grade in breast cancers associated with hormone use [corrected] do not differ significantly from those in non-users, but breast cancers in estrogen-progestin users are significantly more likely to be estrogen receptor (ER) positive. In conclusion, valid evidence from randomized controlled trials (RCTs) indicates that breast cancer risk is increased with estrogen-progestin use more than with estrogen alone. Epidemiological evidence involving more than 1.5 million women agrees broadly with the trial findings. Although new studies are unlikely to alter the key findings about overall breast cancer risk, research is needed, however, to determine the role of progestin, evaluate the risk of lobular cancer and delineate effects of hormone use on receptor presence, prognosis and mortality in breast cancer.     

Review of clinical course and treatment of ovarian hyperstimulation syndrome (OHSS)

The ovarian hyperstimulation syndrome (OHSS) is a rare iatrogenic complication of ovarian stimulation occurring during the luteal phase or during early pregnancy. This complication is unusual as it is not the consequence of a treatment which is vital or mandatory for the patient's health. Nevertheless, it can be accompanied by severe morbidity and may even be fatal. Data pertaining to the clinical course and consequences of OHSS in women and its treatment were searched using Medline, Current Contents and PubMed. To date, only a few studies have collected a large number of cases of OHSS. The clinical course of OHSS may involve, according to its severity and the occurrence of pregnancy, electrolytic imbalance, neurohormonal and haemodynamic changes, pulmonary manifestations, liver dysfunction, hypoglobulinaemia, febrile morbidity, thromboembolic phenomena, neurological manifestations and adnexal torsion. Treatment of the acute phase relies only on an empirical and symptomatic approach. The general approach will be adapted to the levels of severity. Specific approaches such as paracentesis, pleural puncture, surgical approach of OHSS and specific medication during OHSS were evaluated sporadically. More adequate treatment methods would require a better understanding of the underlying pathophysiological mechanisms, to promote an aetiological therapeutic approach. Properly conducted studies, including large numbers of patients are required in order to determine the best method of prevention and management.     

Unexplained sporadic and recurrent miscarrage in the new millennium: a critical analysis of immune mechanisms and treatments

There have been important advances in basic science investigation of mechanisms underlying spontaneous miscarriages which lend support to empirical treatments such as intravenous immunoglobulin G and allogeneic leukocyte immunotherapy. The results from clinical trials of these and other proposed treatments have been problematic. There is only one published meta-analysis of sufficient power and appropriate stratification to qualify as Level 1 evidence, and that deals only with leukocyte immunotherapy. Here we critically review current trials and their flaws, update the meta-analysis, and comment on potential new approaches. Inadequate sample size, better definition of heterogeneity, and proper stratification to minimize the effects of heterogeneity remain as problems. Verification that the experimental or test treatment was active in producing the expected alteration in immunophysiology in the recipient is lacking in most trials; use of stored rather than fresh allogeneic leukocytes appears problematic. Hidden biases that affect trial significance emerge with critical analysis, and the focus on apparent 'high quality' of design in published reports may be misleading. We conclude that there seem to be enough patients to conduct clinical trials of sufficient size to achieve adequate power to test therapies showing promise in pilot studies, but at present, the only Level 1 evidence concerns leukocyte immunotherapy which appears to increase the chance of a live birth if given to appropriate patients.     

The influence of hydrosalpinx on IVF and embryo transfer: a review

Several retrospective studies have shown an impaired outcomeof IVF in the presence of hydrosalpinx. The retrospective datahave been compiled and presented in meta-analyses, demonstratinga reduction by half in the probability of achieving a pregnancyin the presence of hydrosalpinx and a doubled rate of spontaneousabortion. The main theories trying to explain the underlyingmechanisms have focused on potential embryotoxic propertiesof the fluid or impaired endometrial receptivity to implantation.Several mouse studies have suggested an embryotoxic effect ofthe hydrosalpingeal fluid, a finding which is not supportedin studies on human embryos. It is believed that the fluid exertsa detrimental effect on the endometrium by altering the receptivityor simply by causing a mechanical hindrance for implantation.Different treatment options would then be tubal ligation, salpingostomy,aspiration of hydrosalpinx fluid or salpingectomy. The effectof aspiration has been studied in a few retrospective trialswith contradictory results. Treatment with salpingectomy hasentered into clinical practice without proper evidence for itsbenefit. Concerns have also been raised about the potentialhazard of surgical intervention to ovarian circulation and function.A randomized controlled trial on salpingectomy prior to IVFhas now been conducted as a multicentre study in Scandinavia.Laparoscopic salpingectomy prior to IVF was shown to be beneficialin patients with large hydrosalpinges that were visible on ultrasound,a result which supports the theory of the fluid being involvedin the impaired implantation process.     

Cochrane review: post-operative procedures for improving fertility following pelvic reproductive surgery

The objectives of the study was to determine the effectiveness of post-operative procedures following female pelvic reproductive surgery. A systematic review employing the principles of the Cochrane Menstrual Disorders and Subfertility Group was used. Five randomized controlled trials were included. Participants were women undergoing pelvic reproductive surgery; interventions were any post-operative procedure designed to improve fertility; outcomes were pregnancy, live birth, ectopic pregnancy and miscarriage rates and the rates of tubal patency and procedure-related complications. Summary statistics were expressed as odds ratios. The results showed that the odds of pregnancy, live birth, ectopic pregnancy and miscarriage were not significantly altered by post-operative hydrotubation nor second-look laparoscopy with adhesiolysis. Whether hydrotubation was early or late and whether hydrotubation fluid contained steroid or not had no significant impact on the odds of pregnancy, live birth, ectopic pregnancy or miscarriage. The odds of pregnancy and live birth were significantly increased and infective complications significantly decreased by hydrotubation with fluid containing antibiotic compared with hydrotubation with fluid containing no antibiotic, in late hydrotubation following tubal stent removal 6 weeks after tubal surgery. The odds of at least one patent Fallopian tube were significantly increased with late hydrotubation following tubal stent removal compared with early hydrotubation in women who had no tubal stenting, but this intervention had no significant impact on the odds of pregnancy, live birth, ectopic pregnancy or miscarriage. In conclusion, there is insufficient evidence to support the routine practice of hydrotubation or second-look laparoscopy following female pelvic reproductive surgery. The studies on which this conclusion is based were either poor quality or underpowered. Post-operative hydrotubation with fluid containing antibiotic following tubal surgery may offer benefit over hydrotubation fluid without antibiotic. A randomized controlled trial of post-operative hydrotubation with antibiotic-containing fluid versus no hydrotubation for improving fertility following tubal surgery is justified.     

The present and future state of hormonal treatment for male infertility

Although male factors contribute to over half of all cases of infertility, most infertile men are described as 'idiopathic oligo/asthenozoospermic' rather than diagnosed precisely; hence, specific medical treatment is not possible. One uncommon but treatable cause of male infertility is gonadotrophin deficiency in which gonadotrophin replacement therapy is highly effective at inducing spermatogenesis and fertility. Hormonal therapy is a logical approach for empirical drug therapy given the fundamental role of hormonal regulation in spermatogenesis. However, treatment with GnRH analogues, gonadotrophins, androgens, anti-estrogens, aromatase inhibitors, growth hormone- and prolactin-suppressing drugs is ineffective in unselected infertile men. Prolonged high-dose glucocorticoid therapy for sperm autoimmunity may improve pregnancy rates modestly, but the risks are generally unacceptable compared with IVF or ICSI. For these reasons, modern reproductive technologies, notably ICSI/IVF, have become the de-facto standard empirical treatment of male infertility, despite involving significant though infrequent risks to the fetus and mother. There remains a potential for hormonal methods to improve sperm quality or ultrastructure in subgroups of infertile men more responsive to hormonal manipulation or using novel protein or gene-targeted therapies or biochemical approaches based on post-hormonal receptor mechanisms that stimulate spermatogenesis. How such novel hormonal methods will develop in conjunction with improved ICSI/IVF or cloning technologies, and the potential role of adjunctive hormonal therapy remains to be clarified.     

Neuromotor, cognitive, language and behavioural outcome in children born following IVF or ICSI-a systematic review

BACKGROUND: The effect of in vitro fertilization (IVF) or intracytoplasmicsperm injection (ICSI) on the developing human brain is unclear.The objective of this study is to evaluate neurodevelopmental(ND) outcome of children born following these techniques. METHODS: This systematic review includes studies which compare a groupof children born following IVF/ICSI to children born after naturalconception by assessing outcome in terms of neuromotor development,cognition, speech/language and behaviour. Specific attentionis paid to the studies’ methodological quality based onstudy design, attrition, blinding of the assessor, validityof ND tests used, confounders included and group size or poweranalysis. RESULTS: Twenty-three out of 59 studies had a good methodological qualityincluding 9 register-based (RB) and 14 controlled studies. RBstudies suggested that IVF/ICSI per se does not increase therisk for severe cognitive impairment (i.e. mental retardation)or neuromotor handicaps such as cerebral palsy (CP), the associationof IVF/ICSI and CP being brought about by the association ofassisted conception with risk factors, like preterm birth. Ingeneral, controlled studies of good quality did not report anexcess of ND disorders in IVF/ICSI-children. However, the majorityof studies followed the children during infancy only, therebyprecluding pertinent conclusions on the risk of ND disordersthat come to the expression at older ages, such as fine manipulativedisability or dyslexia. CONCLUSIONS: A negative effect of assisted conception on the developing humanbrain is not identified; however, further research of high methodologicalquality in children beyond pre-school age is needed.     

Gestational surrogacy

Gestational surrogacy is a treatment option available to women with certain clearly defined medical problems, usually an absent uterus, to help them have their own genetic children. IVF allows the creation of embryos from the gametes of the commissioning couple and subsequent transfer of these embryos to the uterus of a surrogate host. The indications for treatment include absent uterus, recurrent miscarriage, repeated failure of IVF and certain medical conditions. Treatment by gestational surrogacy is straightforward and follows routine IVF procedures for the commissioning mother, with the transfer of fresh or frozen-thawed embryos to the surrogate host. The results of treatment are good, as would be expected from the transfer of embryos derived from young women and transferred to fit, fertile women who are also young. Clinical pregnancy rates achieved in large series are up to 40% per transfer and series have reported 60% of hosts achieving live births. The majority of ethical or legal problems that have arisen out of surrogacy have been from natural or partial surrogacy arrangements. The experience of gestational surrogacy has been largely complication-free and early results of the follow-up of children, commissioning couples and surrogates are reassuring. In conclusion, gestational surrogacy arrangements are carried out in a few European countries and in the USA. The results of treatment are satisfactory and the incidence of major ethical or legal complications has been limited. IVF surrogacy is therefore a successful treatment for a small group of women who would otherwise not be able to have their own genetic children.     

Evolution of medical treatment for endometriosis: back to the roots?

Experimental evidence is accumulating to suggest that medicinal botanicals have anti-inflammatory and pain-alleviating properties and hold promise for treatment of endometriosis. Herein, we present a systematic review of clinical and experimental data on the use of medicinal herbs in the treatment of endometriosis. Although there is a general lack of evidence from clinical studies on the potential efficacy of medicinal herbs for the treatment of endometriosis-associated symptoms, our review highlights the anti-inflammatory and pain-alleviating mechanisms of action of herbal remedies. Medicinal herbs and their active components exhibit cytokine-suppressive, COX-2-inhibiting, antioxidant, sedative and pain-alleviating properties. Each of these mechanisms of action would be predicted to have salutary effects in endometriosis. Better understanding of the mechanisms of action, toxicity and herb-herb and herb-drug interactions permits the optimization of design and execution of complementary alternative medicine trials for endometriosis-associated pain. A potential benefit of herbal therapy is the likelihood of synergistic interactions within individual or combinations of plants. In this sense, phytotherapies may be analogous to nutraceuticals or whole food nutrition. We encourage the development of herbal analogues and establishment of special, simplified registration procedures for certain medicinal products, particularly herbal derivates with a long tradition of safe use.     

Laparoscopic myolysis

This review will focus on the different techniques and the long-term effects of the technique called myolysis on myoma growth. Indications for myolysis are essentially pelvic pain, compression symptoms and global uterine volume in order to avoid hysterectomy. In the late 1980s, myolysis was performed laparoscopically with the help of the neodynium: yttrium aluminium garnet (Nd:YAG) laser. Later, bipolar needles were developed as an alternative to the Nd:YAG laser. Diathermy and cryomyolysis were also proposed but series are small in the literature. Very recently, myoma interstitial thermo-therapy (MITT) was performed using the diode laser and a specific optical light diffuser that is designed to transmit laser light in all directions. Laparoscopic myolysis was proved to be effective in provoking myoma shrinkage, with a dramatic decrease in size and a marked devascularization of the myoma and this technique can be proposed as an alternative to myomectomy in selected patients: only those aged >40 years or those not desiring to bear any more children.     

Follow-up studies of children born after frozen sperm donation

The need to assess the health of children born after assisted reproductive technologies (ART) using frozen donor spermatozoa has been a major concern for the last decade. Most available published studies are confusing (since they are retrospective) and refer to small numbers of cases or involve a bias. Two prospective and large population-based studies have been published, one in France and the other in Australia. The general characteristics of children born after ART using frozen spermatozoa was unchanged in comparison with the general population (weight, prematurity, stillbirths, sex ratio). However, the rate of multiple pregnancy was increased, first in artificial insemination with donor semen (AID), where the use of hormonal treatment may be too heavily prescribed, and second in IVF with donor semen (IVF/D) where both the ovulation induction treatments and embryo transfer policy increase the rate of multiple pregnancies. As far as birth defects or chromosomal abnormalities are concerned, no difference has been observed from the general population. Finally, the use of frozen spermatozoa does not seem to affect the health of children conceived by AID or IVF/D. The psychosocial development of such infants is not as well known because of the confidentiality in many countries concerning sperm donation. However, the available information on the psychosocial development of these children up to the age of 8-10 years appears to be reassuring. Larger and longer studies are needed to answer such questions, particularly with regard to adulthood.