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Biomedical subjects

David L Olive

Publications and source records attributed to David L Olive.

At least 19 recordsLinked to original sources
PubMed2007

Two unsuccessful clinical trials on endometriosis and a few lessons learned.

In 1999, a phase II clinical trial on the use of fulvestrant to treat endometriosis was launched; yet after 7 years there is still no report on its outcome. In 2005, another trial on the use of raloxifene to treat endometriosis was terminated early due to unfavorable outcome. The two apparently unsuccessful clinical trials on endometriosis have taught us a few important lessons. First, we need to understand endometriosis through more basic research. We have also been reminded that human endometriosis trials differ from animal studies; anatomy and physiology are often divergent, and outcome measures are certainly different. Ectopic endometrium can differ significantly from eutopic tissue, and this issue needs to be more thoroughly explored. We believe human cell lines will prove to be an inexpensive and valuable tool for future preliminary evaluation of medical therapies as well as discerning pathophysiologic processes of the disease. Based on our current understanding of endometriosis, some concrete benchmarks can be established for testing or screening potential compounds in vitro. Finally, estrogen receptor modulators are often tissue-, cell-, and context-specific in their actions; they should not be simplistically grouped together nor should extrapolations from one compound to another be undertaken in a cavalier manner.

Adult↗
PubMed2006

Comparative assessment of pre- and post-donation attitudes towards potential oocyte and embryo disposition and management among ovum donors in an oocyte donation programme.

BACKGROUND: In anonymous oocyte donation programmes, the disposition of retrieved oocytes and subsequent embryo management are at the discretion of the IVF programme and the oocyte recipients, as donors waive all rights following their donation. Nonetheless, donors are routinely made aware of ways in which oocytes and resulting embryos may be used and elect to proceed with the process even in the presence of reservations to some clinical scenarios before their donation. The aim of our study was to examine oocyte donors' attitudes to oocyte and embryo disposition and management and how initial reservations change over the course of the donation process. METHODS: Oocyte donors in a university-based IVF programme were asked about their willingness to donate in relation to various clinical scenarios during the initial screening interview and at the post-donation exit interview. Results were tabulated as 'yes' or 'no'. RESULTS: At the pre-donation interview, 72% of donor candidates expressed reservations to one or more clinical scenarios. More reservations were expressed at the post-donation interview compared with the pre-donation interview. The greatest reservations were donating to recipients >50 years of age (P < 0.05). Despite this, 97% of donors were willing to donate again. CONCLUSION: Oocyte donors' attitudes towards various clinical scenarios changed following their donation, reflecting overall greater reservations following the donation process. Although speculative, donors may be more willing to assert their opinions or donor attitudes become more restrictive.

Adult↗
PubMed2006

Estimating infertility: the devil is in the details.

Self-reported data have serious limitations, particularly when the outcome is constructed from indirect questions. Policy decisions require clearly defined issues, validated tools, careful and comprehensive analysis, and cautious interpretation.

Adolescent↗
PubMed2006

Conservative surgical management of uterine myomas.

Uterine fibroids are a major gynecologic problem in American women, and several alternatives have been developed. Conservative treatment, with the goal of treating the fibroid but retaining the uterus, is a frequent choice among women who require therapy during their early to middle reproductive years. A variety of conservative surgical approaches exist; each has advantages and disadvantages for the clinician and the patient. Some are well-established techniques, whereas others are still in the investigational stage. None has been evaluated adequately for its effects on future fertility. To this end, it is imperative that investigators continue to evaluate these surgical procedures so that the clinician can provide accurate and comprehensive information when faced with a patient who desires one or more of these approaches. Furthermore, it is critical for the practitioner to stay informed about these procedures so that patients can be given a full complement of options.

Clinical Trials as Topic↗
PubMed2006

Investigational drugs for endometriosis.

Endometriosis is an enigmatic disease found in as many as 30% of reproductive age women. The symptoms for women who suffer from this malady vary but may include subfertility or chronic pelvic pain. Because endometriosis lesions rely on estradiol for growth, most of the existing drug regimens work by creating hypoestrogenism. Unfortunately, this leads to untoward side effects and alterations in ovulation and, subsequently, fertility potential. Newer drugs are currently under investigation that either create hypoestrogenemia more efficaciously or do not alter ovulation but still affect the growth of endometriosis. They target some of the pathophysiological pathways that are only now being elucidated, and include gonadotropin-releasing hormone antagonists, aromatase inhibitors, selective progesterone receptor modulators, angiogenesis inhibitors, matrix metalloprotease inhibitors, estrogen receptor beta-agonists and immune modulators.

Aromatase Inhibitors↗
PubMed2005

Assessment of wishes regarding disposition of oocytes and embryo management among ovum donors in an anonymous egg donation program.

Revealing possible clinical scenarios to potential anonymous donors for their donated oocytes appears to uncover ambivalence in the majority of prospective candidates about their donation and unwillingness in some to proceed. Full disclosure to a prospective donor candidate of the program's policies for directives of donated oocytes and embryo management emphasizes the importance of the informed consent process and how it may affect the decision to donate.

Adult↗
PubMed2005

Serum dioxin concentrations and age at menopause.

2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD), a halogenated compound that binds the aryl hydrocarbon receptor, is a by-product of numerous industrial processes including waste incineration. Studies in rats and monkeys suggest that TCDD may affect ovarian function. We examined the relationship of TCDD and age at menopause in a population of women residing near Seveso, Italy, in 1976, at the time of a chemical plant explosion. We included 616 of the women who participated 20 years later in the Seveso Women's Health Study. All women were premenopausal at the time of the explosion, had TCDD levels measured in serum collected soon after the explosion, and were > or = 35 years of age at interview. Using proportional hazards modeling, we found a 6% nonsignificant increase in risk of early menopause with a 10-fold increase in serum TCDD. When TCDD levels were categorized, compared with women in the lowest quintile (< 20.4 ppt), women in quintile 2 (20.4-34.2 ppt) had a hazard ratio (HR) of 1.1 (p = 0.77), quintile 3 (34.3-54.1 ppt) had an HR of 1.4 (p = 0.14), quintile 4 (54.2-118 ppt) had an HR of 1.6 (p = 0.10), and quintile 5 (> 118 ppt) had an HR of 1.1 (p = 0.82) for risk of earlier menopause. The trend toward earlier menopause across the first four quintiles is statistically significant (p = 0.04). These results suggest a nonmonotonic dose-related association with increasing risk of earlier menopause up to about 100 ppt TCDD, but not above.

Adolescent↗
PubMed2005

Empirical therapy with leuprorelin acetate for endometriosis in the United States.

Trends in the use of laparoscopy as a diagnostic and treatment tool for endometriosis are changing in the United States and the use of empirical treatment for chronic pelvic pain is on the rise. Although it is regarded as the gold standard for the diagnosis of endometriosis, laparoscopy has a positive predictive value of only 43-45%. Furthermore, chronic pelvic pain can be treated medically without a diagnosis confirmed by laparoscopy and histology. Therapy with the gonadotropin-releasing hormone (GnRH) agonist leuprorelin acetate is effective in relieving pelvic pain regardless of the presence of endometriosis. The current treatment algorithm for chronic pelvic pain in the United States comprises physical examination, medical history and ultrasound, and if the cause of the pain is not identified, treatment with oral contraceptives and nonsteroidal antiinflammatory drugs is undertaken. On lack of response to these treatments, GnRH agonist therapy is initiated. The American College of Obstetrics and Gynecology supports therapy with GnRH agonists in the management of women with chronic pelvic pain, even in the absence of confirmation of endometriosis, provided that a detailed investigation reveals no other cause of the pain. Laparoscopy is the final option if pain is not relieved by medical treatments.

Endometriosis↗
PubMed2005

The role of add-back therapy in the United States.

Gonadotropin-releasing hormone (GnRH) agonists are effective in reducing pelvic pain due to endometriosis, but they are associated with a number of hypoestrogenic side effects, such as vasomotor symptoms and loss of bone mineral density. Add-back therapy with a progestin or a progestin plus low-dose estrogen helps to reduce the side effects associated with GnRH agonist administration without compromising efficacy. Add-back therapy should be initiated at the same time as the treatment with a GnRH agonist and longer-term therapy beyond 6 months can be considered in patients meeting the appropriate criteria.

Endometriosis↗
PubMed2004

New medical treatments for endometriosis.

The medical treatment of endometriosis has long centered upon producing a hypoestrogenic environment by producing pituitary suppression or a progestin-dominant environment. However, as more is uncovered regarding the pathogenesis and pathophysiology of this disease, more targeted therapies can be developed. Current research has focused upon medications designed to attack specific aspects of the development and maintenance of endometriosis. These include progesterone receptor modulators, gonadotropin releasing hormone (GnRH) antagonists, aromatase inhibitors, tumor necrosis factor alpha (TNF-alpha) inhibitors, angiogenesis inhibitors, matrix metalloproteinase inhibitors, pentoxifylline (and other general immune modulators), and estrogen receptor beta agonists. It is hoped that this new wave of medications will improve the response to medical therapy for this disorder.

Angiogenesis Inhibitors↗
PubMed2004

Evaluation of risk factors associated with endometriosis.

OBJECTIVE: To investigate the association between several factors such as demographics, personal habits, reproductive factors, menstrual characteristics, contraception, and clinical profile and the probability of having endometriosis. SETTING: Ten clinical institutions in the Montreal area. PATIENT(S): A total of 2777 subjects who underwent surgery for diagnostic laparoscopy, tubal ligation, or hysterectomy between January 1998 and July 2002. Eight hundred ninety subjects were classified as cases on the basis of the presence of endometriotic lesions found at the time of surgery, whereas 1881 controls had no surgical evidence of endometriosis. MAIN OUTCOME MEASURE(S): The association between potential risk factors and endometriosis was estimated by Pearson chi(2) and by crude and adjusted odds ratios. RESULT(S): Results indicated a positive association between endometriosis and education level for subjects who underwent hysterectomy. An inverse relation between gravidity and endometriosis was also found within a subgroup of subjects who had diagnostic laparoscopy. Furthermore, the proportion of uterine leiomyoma was significantly higher in cases compared with in controls, among subjects who underwent surgery for diagnostic laparoscopy or hysterectomy but not for tubal ligation. CONCLUSION(S): These observations underline the importance of taking into account the clinical profile of subjects when investigating risk factors for endometriosis.

Educational Status↗
PubMed2004

Non-surgical management of leiomyoma: impact on fertility.

PURPOSE OF REVIEW: This review is designed to discuss the literature, published from December 2002 to January 2004, on the non-surgical treatment of fibroid. All established and new modalities are reviewed, and all new developments in the field are discussed. The resulting impact on the treatment of infertility will also be evaluated. RECENT FINDINGS: In the past year important advances occurred in the medical treatment of uterine fibroids. It was found, in a large randomized trial, that preoperative treatment with gonadotropin-releasing hormone analogue did not improve surgical results or decrease blood loss. However, important strides were made in understanding the molecular biology of the effect of the hormone analogue on fibroids. Other medical therapies investigated include danazol, raloxifene, mifepristone, aromatase inhibitors, and the levonorgestrel-containing intrauterine device. Most promising in terms of long-term usage for reduction of size and symptoms appears to be the combination of gonadotropin-releasing hormone analogue and raloxifene, although selective progesterone receptor modulators may also achieve this aim. However, none avoid producing an anovulatory state that inhibits fertility, and none have been shown to enhance fertility following discontinuation. Uterine artery embolization is another non-surgical technique under intense investigation. The year's literature suggests that while results are comparable with hysterectomy in terms of complication rate and patient satisfaction, there may be important issues for women who wish to undergo the procedure and retain future fertility. Specifically, there is a significant rate of premature ovarian failure, as well as occasional damage to the endometrial vasculature with resulting atrophy and adhesion formation. Improvements in technique, in particular the use of larger and more spherical microspheres for embolization, may reduce these unwanted effects. However, few data exist regarding the course of pregnancy and outcome following embolization. SUMMARY: A number of non-surgical treatments exist for uterine fibroids, but none has been shown to be of value in the patient desiring future fertility. Myomectomy remains the standard of care for such women, and all other therapies should be designated experimental and limited to appropriate investigational studies.

Embolization, Therapeutic↗
PubMed2004

Optimizing gonadotropin-releasing hormone agonist therapy in women with endometriosis.

Endometriosis is a highly prevalent disease among women of reproductive age. While many treatments are available, one of the most widely utilized is treatment with gonadotropin-releasing hormone (GnRH) agonists. These agents work by producing a profound suppression of gonadotropin secretion by the pituitary, resulting in a hypoestrogenic state and subsequent diminution of endometriosis lesions. The GnRH agonists on the market have been shown to work quite well in reducing all pain symptoms associated with endometriosis, including dysmenorrhea, dyspareunia, and noncyclic pelvic pain. However, there is no evidence to suggest that this treatment is of value in endometriosis-associated infertility. Conflicting data exist regarding the role of GnRH agonists in the treatment of endometriomas, but the bulk of the evidence suggests a low degree of efficacy. GnRH agonists are often initiated with the onset of menses, but a more rapid response is observed with mid-luteal administration. A limit of 6 months per treatment course is required due to loss of bone mineral density during therapy, but this can be extended via the addition of 'add-back' therapy. Such adjunctive regimens demonstrated to maintain efficacy and reduce adverse effects include progestogen alone or a low-dose combination of estrogen and progestogen. Retreatment with these drugs is supported by limited data. The use of GnRH agonists as surgical adjuncts has been studied by several investigators. Their use preoperatively has not been shown to be of value. Similarly, 3 months of postoperative administration has failed to enhance treatment. However, 6 months of postoperative GnRH agonists appear to improve the duration of relief of pain symptoms. Future studies will need to focus on the role of these agents when used for repeated courses, in young women, and in conjunction with assisted reproduction.

Combined Modality Therapy↗