Changes in patient preferences in the disposal of cryopreserved embryos.

BACKGROUND: The disposal of unused cryopreserved embryos can be a difficult decision for patients and the existence of unclaimed embryos raises ethical concerns for clinics. This study examined changes in patients' preferences for disposition of unused embryos and the relevance of a two-stage process for obtaining consent. METHODS: Patients who had not returned for cryopreserved embryos for over 5 years were contacted and asked to specify their current preferences for embryo disposition. These preferences were compared with dispositional choices made at the time of embryo freezing. RESULTS: Over one-third of patients had not returned for cryopreserved embryos within 5 years, and 31% of these declined to provide an updated directive. Those with a live birth through treatment were more likely to provide a new directive and more likely to choose to discard rather than donate embryos for research. Prior to IVF, the majority of non-returnees had elected to donate unused embryos for research, but 59% of all couples changed their minds after treatment. CONCLUSIONS: Changes in preferences for embryo disposition was linked to treatment outcome and highlighted the need for a two-stage process to obtain fully informed consent. In this Canadian sample, patients' affinity for research declined after treatment.

Sperm donation: implications of Canada's Assisted Human Reproduction Act 2004 for recipients, donors, health professionals, and institutions.

BACKGROUND: On April 22, 2004, the Assisted Human Reproduction Act came into force, prohibiting the purchase of sperm or eggs from donors in Canada. In response to the concerns of medical professionals and some consumers that prohibiting payment would lead to a decline in the number of gamete donors, Health Canada commissioned research on altruistic donor recruitment and recruitment strategies. METHODS: Twenty-two studies of sperm donors were located and their findings reviewed. The studies spanned 23 years (1980-2003), were undertaken in a range of countries, and were chosen on the merit of their relevance to the development of recruitment strategies within a policy of altruistic sperm donation. Observations were derived from assessing and comparing the purposes, findings, and implications of the 22 studies. RESULTS: Payment for providing sperm was made in all but three studies, although participants in 15 studies indicated clearly that their motivations were primarily altruistic. Observations indicate that men who are more willing to be identified to offspring in the future share demographic characteristics, such as age and parental status, with those who are prepared to donate altruistically. These characteristics appear to be a factor in motivation to donate altruistically. CONCLUSION: The studies show that there are men who are prepared to donate sperm without financial payment. The findings suggest that a change is required in the culture of sperm donation, specifically the adoption of a new approach to donor recruitment.

Poor responders in assisted reproduction cycles.

Poor responders represent a challenging group of infertility patients who fail to respond to controlled ovarian hyperstimulation during the course of assisted reproduction treatment. Although poor response has been investigated since the eighties, many aspects of this condition are still controversial and no consensus has been reached on the management of these patients. The existing data cannot be easily compared due to the heterogeneity of the research design and methodology and the number of prospective randomized trials of sufficient sample size is limited. In addition, more research in the identification and understanding of underlying factors is needed together with a better understanding of the patho-physiological basis of ovarian ageing and of the progressive reduction in ovarian reserve. This paper provides an overview on the identification, prediction and management of poor responders undergoing medicated assisted reproduction treatment.

Endometriosis related to infertility.

Endometriosis is a disease affecting the physical health and emotional well being of many women worldwide. General estimates indicate that at least 25% of all women in their 30s and 40s may be suffering from endometriosis and 30-50% of the affected women are also infertile. Medical therapy, surgery and assisted reproduction are the 3 main options available to women affected by this condition. The etiology and pathophysiology of endometriosis-associated infertility are still obscure, despite an enormous effort over many decades. The management of this disease is a source of controversy and so far no consensus has been reached. Most studies show considerable variation in methodology, may not have enough statistical power or report results that are exactly the opposite of what has been previously published. In light of the disagreement that surrounds the study of endometriosis-associated infertility, a new comprehensive multi-centre study should be designed with the international collaboration of all major experts in this field.

Premenstrual syndrome.

Premenstrual syndrome (PMS) affects the quality of life of millions of women. The complexity and variety of clinical presentation together with the cyclic recurrence of affective and somatic symptoms increase the difficulty in understanding and treating the disease. The precise pathophysiology of PMS is still unknown, but it is increasingly believed that, in women with PMS, the sensitive equilibrium between sex-steroids and central neurotransmitters is altered. Several studies have been carried out to understand the origin of the syndrome and to discover new ways of treatment. This review summarizes the most accepted PMS theories and treatments currently available based on the results of the best-designed trials.

Effects of progestins on progesterone synthesis in a stable porcine granulosa cell line: control of transcriptional activity of the cytochrome p450 side-chain cleavage gene.

The purpose of the present study was to examine the effects of progestins on progesterone synthesis and expression of the cytochrome P450 cholesterol side-chain cleavage gene (P450(scc)) in a stable porcine granulosa cell line, the JC-410. Cells were incubated for 48 h with the synthetic progestogen-levornorgestrel with or without RU486 (progesterone and glucocorticoid receptor antagonist) or RWJ26819 (progesterone agonist without affinity to glucocorticoid receptors). Both levonorgestrel and RU486 enhanced progesterone accumulation in a dose-dependent manner. RU486 did not antagonize the effects of levonorgestrel, and RWJ26819 had no effect on progesterone production in cultured JC-410 cells. Progesterone and levonorgestrel increased steady state P450(scc) mRNA levels after 3-6 h of treatment. Progesterone and RU486 at 0.1, 1, and 10 microM increased the transcription rate of P450(scc) transiently expressed in JC-410 cells after 18 h of incubation; 30 microM had no effect, and 100 microM suppressed transcription. Levonorgestrel did not affect transcription of the P450(scc) gene, and RWJ26819 reduced its transcription. Progesterone and RU486 significantly decreased the number of cells and total protein content after 72 and 24 h of incubation, respectively. Levonorgestrel had no effect, whereas RWJ26819 increased (24 h) but subsequently reduced (72 h) cell number and protein content. The present results indicate that progestins are capable of directly modulating progesterone biosynthesis in porcine JC-410 granulosa cells. These effects may be exerted in part through the regulation of P450(scc) gene expression. Ostensible differences exist between progesterone and its synthetic analogues in the control of progesterone secretion in the stable porcine granulosa cell line in vitro.

Association between mutations of the follicle-stimulating-hormone receptor and repeated twinning.

Follicle-stimulating hormone (FSH) has a role in folliculogenesis and spontaneous twinning. Using the candidate gene approach, we searched for mutations in the gene encoding the FSH receptor in a woman who had given birth to two sets of dizygotic twins without fertility treatment. We identified two linked mutations (Thr307Ala and Asn680Ser) that were closely associated with this phenotype. We suggest that expression of both mutations increases the sensitivity of the receptor to FSH.

Recurrent pregnancy loss associated with endometrial hyperechoic areas (endometrial calcifications): a case report and review of the literature.

Endometrial calcifications occur sporadically and are associated with infertility. Previous uterine trauma during instrumentation and/or uterine infection are likely involved in their pathogenesis. The association between endometrial calcifications and recurrent pregnancy loss has been very infrequently reported. A 28-year-old woman with a history of two consecutive first trimester pregnancy losses presented with ultrasonographic hyperechoic endometrial areas associated with histologic endometrial calcification foci. A third pregnancy conceived before starting micronized oral progesterone supplementation also spontaneously aborted at eight weeks. During the fourth pregnancy, progesterone supplementation was taken for the initial 12 weeks. The endometrial lesions were no longer detectable and the pregnancy progressed to term without complications. Endometrial calcifications, related to intrauterine bone tissue, have been previously treated with curettage or with endoscopic surgery, and to the best of our knowledge, have not been reported to disappear spontaneously. In this case, regression of the endometrial calcifications and a favorable pregnancy outcome occurred in concert with oral micronized progesterone supplementation. A combination of transvaginal ultrasonography and endometrial biopsy appears to be an effective method for diagnosing and monitoring of this rare condition.

Future in vitro fertilization pregnancy potential of women with variably elevated day 3 follicle-stimulating hormone levels.

OBJECTIVE: To determine the IVF-ET pregnancy potential of women with variably elevated day 3 FSH. DESIGN: Cohort evaluation of 1,868 consecutive IVF-ET cycles January 1991 to December 1994. SETTING: University hospital infertility unit. PATIENTS: Four cohorts of couples were defined based on day 3 FSH determinations with an arbitrary threshold of 20 mIU/mL, only > or = 20 mIU/mL, always < 20 mIU/mL, current < 20 mIU/mL but one previous > or = 20 mIU/mL, and current < 20 mIU/mL but two or more previous > or = 20 mIU/mL (conversion factor to SI unit, 1.00). INTERVENTION: In vitro fertilization-embryo transfer. MAIN OUTCOME MEASURE: Fetal heart activity on luteal day 40 transvaginal ultrasound. RESULTS: No pregnancies occurred in 53 cycles with day 3 FSH only > or = 20 mIU/mL. In 1,750 women whose day 3 FSH levels were always < 20 mIU/mL, the pregnancy rate (PR) per cycle was 16.5%. In 54 cycles in which day 3 FSH was > or = 20 one time only, but < 20 mIU/mL during the treatment cycle, the PR was 5.6%. In 11 cycles where two or more previous FSH determinations were > or = 20 mIU/mL but with a current day 3 FSH < 20 mIU/mL, no pregnancies occurred. CONCLUSION: Our data leads us to the conclusion that day 3 FSH determination precede every IVF cycle and that cycles with FSH > or = 20 mIU/mL be canceled. It also suggests that women with two previous elevations of day 3 FSH be discouraged from future IVF cycles. The 5.6% pregnancy per cycle with one previously elevated FSH warrants extreme pessimism in discussion of further cycles.

Induced morphological changes in human small cell lung carcinoma cells.

Several theories suggest that lung carcinomas are not totally separate entities, but are derived from a common precursor, probably of endodermal origin. The histological classification of lung cancers is complex, with much overlap between groups broadly designated as small cell (SCLC), squamous cell, adenocarcinoma and all others simply termed non-small cell. It is shown here that in vitro exposure of classic, non-adherent SCLC lines to 10 microM 5' bromodeoxyuridine (BrdU) results in a rapid cell-line dependent change to a morphology consistent with an adherent, non-small cell phenotype. Accompanying this morphological shift is a decreased expression of the amplified N-myc protooncogene. These induced changes underline the morphological relatedness of lung carcinoma cell lines.