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Query: UMLS:C0021359 (infertility)
 26,075 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this review is to examine whether the time has come to replace clomiphene citrate (CC) as the first line therapy for WHO group II (eu-oestrogenic) infertility, the majority of which is associated with polycystic ovary syndrome. CC has been the first line therapy for these cases for the last 40 years. It is a simple, cheap treatment, almost devoid of side effects which yields a single live birth rate of approximately 25% of starters. Non-response to CC and the gap between ovulation and pregnancy rates have variously been attributed to its anti-estrogen effects, and high LH and androgen concentrations. Three possible contenders for the replacement of CC as first-line treatment are scrutinized: metformin, aromatase inhibitors and low-dose FSH. Each has their advantages and disadvantages, but none of them, while showing much potential promise, has been proven, as yet, to be a feasible replacement for CC in this role. For CC, it may not yet be the end of an era but it may be the beginning of the end.
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PMID:Clomiphene citrate--end of an era? A mini-review. 1587 25

Aromatase inhibitors (AI) block the last enzymatic step of estrogen production, the aromatization of the A-cycle of aromatizable androgens and particularly, androstenedione (D4) and testosterone (T). Molecules designed for interfering with aromatase activity have existed for many years. Yet the activity of products of the aminogluthetimide era was too unspecific and these substances carried too many side effects for being used clinically. Today, however, 3rd generation AIs have become available that are highly specific and essentially devoid of side effects. These molecules have recently been approved for treating breast cancer in post-menopausal women, either in advanced forms, or as part of adjuvant therapy. In women whose ovaries are active, a temporary inhibition of E2 production will activate gonadotropins and in turn, stimulate follicular growth. In cancer patients, this property precludes the use of AIs in women whose ovaries are still active, unless gonadotropins are blocked. In infertile patients, this property of AIs has been put to play for inducing ovulation. AIs have been used both in women who do not ovulate but whose hypothalamo-pituitary-gonadal (HPG) axis is active (oligo-anovulators of PCOD type) and in those who ovulate regularly but in whom multiple ovulation is sought for treating infertility or as part of IVF. Like CC, AIs are not usable in women whose gonadotropins are suppressed, as in the case of hypothalamic amenorrhea. The sum of data available on the use of AI for inducing ovulation remains however meager to this date and is mainly constituted of pilot and non-randomized trials. Yet mounting evidence tends to support AIs' advantages over CC for induction of ovulation. Hence, we think that these drugs will play a key role for the induction of ovulation in the future.
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PMID:[Use of aromatase inhibitors in infertile women]. 1614 May 57

Aromatase inhibitors (AI) block the last enzymatic step of estrogen production, the aromatization of the A-cycle of aromatizable androgens and particularly, androstenedione (delta4) and testosterone (T). Molecules designed for interfering with aromatase activity have existed for many years. Yet the activity of products of the aminogluthetimide era was unspecific and these substances carried too many side effects for being used clinically. Newer third generation AIs, however, are highly specific and essentially devoid of side effects. These molecules have recently been approved for treating breast cancer in postmenopausal women either, in advanced forms or, as part of adjuvant therapy. In women whose ovaries are active, a temporary inhibition of E2 production will raise gonadotropins and in turn, stimulate follicular growth. In cancer patients, this property precludes the use of AIs in women whose ovaries are still active, unless gonadotropins are blocked. But in infertility patients, this property of AIs has been put to play for inducing ovulation. AIs have been used both in women who do not ovulate but whose hypothalamo-pituitary-gonadal (HPG) axis is active (oligo-anovulators of PCOD type) and those who ovulate regularly but in whom multiple ovulation is sought for treating unexplained infertility or as part of IVF. Like clomiphene citrate (CC), AIs are not usable in women whose gonadotropins are suppressed, as in the case of hypothalamic amenorrhea. The sum of data available on the use of AI for inducing ovulation remains however meager to this date and is mainly constituted of pilot and non-randomized trials. Yet mounting evidence tends to support AIs' advantages over CC for induction of ovulation. Hence, we think that the likelihood that these drugs will play a key role in induction of ovulation in the future is high. AIs appear particularly interesting for treating unexplained infertility because AI-FSH/hMG regimens are lighter than FSH-only regimens while retaining the high pregnancy rates of these latter treatments.
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PMID:Clinical use of aromatase inhibitors (AI) in premenopausal women. 1868 52

Ovulation induction is the method for treating anovulatory infertility. For patients with hypogonadotrophic hypogonadism, the treatment involves administration of both FSH and LH, while HCG is injected for follicle rupture. Pulsatile GnRH has the same effectiveness as gonadotrophins and the advantage of the low multiple pregnancy rate. In polycystic ovary syndrome (PCOS), the first treatment choice is clomiphene citrate. With this drug, in properly selected patients, the cumulative pregnancy rate approaches that of normal women. Low-dose protocols of FSH are the second line of treatment, effective in inducing monofollicular development. Laparoscopic ovarian drilling can be an alternative but not as a first choice treatment in clomiphene-resistant patients. Other treatments, such as pulsatile GnRH and GnRH agonists, are hardly used today in PCOS. However, in obese women with PCOS, weight loss and exercise should be recommended as the first line of therapy. Newer agents including aromatase inhibitors and insulin sensitizers, although promising, need further evaluation.
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PMID:Ovulation induction: a mini review. 1600 78

Endometriosis is a common, chronic and estrogen-dependent gynaecological disorder associated with pelvic pain and infertility. In addition to, or perhaps as a consequence of, immune, environmental and genetic factors, endometriotic lesions show high estradiol (E(2)) biosynthesis and low E(2) inactivation compared with normal endometrium. Current medical therapies of pain, which aim to lower circulating E(2) concentrations, are not effective in at least half of these patients. We and others recently demonstrated the expression of a few steroidogenic genes in endometriosis. The most important genes in this group are steroidogenic acute regulatory protein (StAR) and aromatase. Both are essential for E(2) production. Prostaglandin E(2) (PGE(2)) is the most potent known stimulator of both StAR and aromatase. PGE(2) production in endometriosis is up-regulated by increased levels of the enzyme cyclo-oxygenase-2 (COX-2) in this tissue. COX-2 in turn is stimulated by E(2), interleukin-1beta (IL-1beta) and PGE(2) itself in endometrial and endometriotic cells. Thus, there is a positive feedback loop that favours continuous formation of E(2) and PGE(2) in endometriosis. These basic findings led to recent phase-II studies employing aromatase inhibitors in the treatment of endometriosis. Aromatase inhibitors treat both postmenopausal and premenopausal endometriosis at least as effectively as the existing medical treatments. In premenopausal women, we and others administered aromatase inhibitors in combination with an ovarian-suppressant treatment. In this review, we emphasize the most recent basic studies in detail and provide a short summary of recent clinical trials.
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PMID:Aromatase and other steroidogenic genes in endometriosis: translational aspects. 1612 52

Conventional treatment of normogonadotropic anovulatory infertility is ovulation induction using the antiestrogen clomiphene citrate, followed by follicle-stimulating hormone. Multiple follicle development, associated with ovarian hyperstimulation, and multiple pregnancy remain the major complications. Cumulative singleton and multiple pregnancy rate data after different induction treatments are needed. Newer ovulation induction interventions, such as insulin-sensitizing drugs, aromatase inhibitors and laparoscopic ovarian electrocoagulation, should be compared with conventional strategies. Ovulation induction efficiency might improve if patient subgroups with altered chances for success or complications with new or conventional techniques could be identified, using multivariate prediction models based on initial screening characteristics. This would make ovulation induction more cost-effective, safe and convenient, enabling doctors to advise patients on the most effective and patient-tailored treatment strategy.
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PMID:Patient-tailored conventional ovulation induction algorithms in anovulatory infertility. 1612 15

The management of infertility in women with polycystic ovary syndrome (PCOS) centers around options for inducing ovulation. This is an evidence-based review of the management of PCOS, which includes a MEDLINE search of publications between 1986 and May 2005 and a search of the Cochrane Database. Weight loss, exercise, and metformin will induce ovulation in many insulin-resistant women and obese women with PCOS, and should always be the first-line treatment. Ovulation induction has been performed with clomiphene citrate (clomifene) as the first-line treatment, but the use of aromatase inhibitors has been shown to be as successful. The strategies for reducing the risks of gonadotropin therapy such as low-dose follicle-stimulating hormone (FSH) stimulation and the addition of metformin are discussed. Both gonadotropin releasing-hormone agonists and antagonists are equally effective in in vitro fertilization stimulation in conjunction with FSH therapy. Metformin may have a benefit in pregnancy in reducing the risks of miscarriage and diabetes mellitus; however, prospective trials are still lacking.
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PMID:Management of infertility in women with polycystic ovary syndrome : a practical guide. 1618 97

Our previous studies have shown that transgenic male mice expressing human P450 aromatase (AROM+) are infertile. In the present study, we followed the testis phenotype up to 15 months of age in these mice. The testes of the old AROM+ mice showed Leydig cell hypertrophy and hyperplasia, as indicated by the staining for steroidogenic enzymes and androgen and estrogen receptors. However, the Leydig cell adenomas did not show signs of malignization. In contrast, we observed a marked increase in the number of activated macrophages in the testicular interstitium of the aging AROM+ mice. The macrophages were further shown to express high levels of CD68 (a monocyte/macrophage marker) and secrete TNFalpha, indicating strong activation, presumably by estrogen exposure. The increased activity of the macrophages was associated with Leydig cell depletion (analyzed at the age of 9 and 15 months) and an increased number of mast cells and fibrosis in the testicular interstitium. Interestingly, similar findings have been made in testes of infertile men. Hence, the aging AROM+ males present with a phenocopy of inflammation-associated infertility in men, providing a model for further studies on the putative link among estrogens, orchitis, and infertility.
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PMID:Transgenic mice expressing p450 aromatase as a model for male infertility associated with chronic inflammation in the testis. 1630 85

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by hirsutism, obesity, hyperandrogenism and insulin resistance. The syndrome is often accompanied by infertility because of anovulation. Many approaches have been proposed to solve this problem, with the most commonly used therapies being ovarian drilling and pharmacological ovulation induction. Ovarian drilling is a procedure in which a laser fiber or electro-surgical needle punctures the ovary four to ten times. Side-effects are rare and often related to surgery itself. Pharmacological strategies include administration of metformin and insulin-sensitizing agents, clomiphene citrate (CC), gonadotropins and aromatase inhibitors. Metformin appears valuable in increasing ovulation rate, menstrual cyclicity and pregnancy rate. CC is an oral estrogen antagonist that raises circulating concentrations of follicle-stimulating hormone (FSH) and induces follicular growth in most women with PCOS and anovulation. Failure to respond is associated with high body mass index and high androgen levels. Aromatase inhibitors mimic the central reduction of negative feedback through which CC works. Ovulation induction with recombinant FSH has proved successful, but treatment requires skill and experience to avoid multiple pregnancies and ovarian hyperstimulation syndrome. The hypothetical deleterious effects of the high luteinizing hormone concentrations observed in PCOS patients seem to be related to the concomitant hyperinsulinemia (and/or insulin resistance). A thorough understanding of the syndrome and a careful assessment of each patient are the mainstays for choosing an appropriate treatment regimen.
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PMID:Therapeutic strategies for ovulation induction in infertile women with polycystic ovary syndrome. 1639 Jul 83

In recent years a dynamic development of research on endometriosis has been observed. Complex and not definitively recognized etiopathogenesis, impedes diagnostic progress and effective treatment. Frequent incidence of endometriosis in reproductive age and high percentage of the illness in the group of patients with infertility, both determine the importance of that issue. The article below presents the latest lines of research on efficient therapeutical scheme, covering reproductive abilities. Attempts of implementation of aromatase inhibitors, selective estrogen receptor modulators, immunomodulators and antiinflammatory agents have been described. Considering groups of medicines mentioned in the article, the outcome of examination using aromatase inhibitors, immunomodulators mainly IL-2, INF-alpha-2b, as well as antiinflammatory agents--recombinant human TNF binding protein-1, seem to be most encouraging. Part of the survey was conducted on animal models therefore it requires verification of usefulness and effectiveness on people. The results are very promising, they set the trend of future research aimed at application of modern and efficient treatment of endometriosis.
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PMID:[Perspectives of endometriosis treatment]. 1652 40


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