Journal of experimental & clinical assisted reproduction最新文献

Background: This research describes current clinical and demographic features sampled from reproductive endocrinology programs currently offering in vitro fertilization (IVF) in the Middle East.

Methods: Clinic leadership provided data via questionnaire on patient demographics, demand for IVF services, annual cycle volume, indications for IVF, number of embryos transferred, twinning frequency, local regulations governing range of available adjunct therapies, time interval between initial enrollment and beginning IVF as well as information about other aspects of IVF at each center.

Results: Data were received from representative IVF clinics (n = 13) in Cyprus, Egypt, Iran, Israel, Jordan, Lebanon, Qatar, Saudi Arabia and Turkey. Mean (+/- SD) age of respondents was 47.8 +/- 8 yrs, with average tenure at their facility of 11.2 +/- 6 yrs. Estimated total number of IVF programs in each nation responding ranged from 1 to 91. All respondents reported individual participation in accredited CME activity within 24 months. 76.9% performed embryo transfers personally; blastocyst transfer was available at 84.6% of centers. PGD was offered at all sites. In this population, male factor infertility accounted for most IVF consultations and the majority (59.1%) of female IVF patients were < 35 yrs of age. Prevalence of smoking among female IVF patients was 7.2%. Average number of embryos transferred was 2.4 (+/- 0.4) for patients at age < 35 yrs, and 2.9 (+/- 0.8) at age > 41 yrs. For these age categories, twinning (any type) was observed in 22.6 (+/- 10.8)% and 13.7 (+/- 10.4)%, respectively. In 2005, the average number of IVF cycles completed at study sites was 1194 (range 363-3500) and 1266 (range 263-4000) in 2006. Frozen embryo transfers accounted for 17.2% of cycles at these centers in 2005. Average interval between initial enrollment and IVF cycle start was 8 weeks (range 0.3-3.5 months).

Conclusion: This sampling of diverse IVF clinics in the Middle East, believed to be the first of its kind, identified several common factors. Government registry or oversight of clinical IVF practice was limited or nonexistent in most countries, yet number of embryos transferred was nevertheless fairly uniform. Sophisticated reproductive health services in this region are associated with minimal delay (often < 8 weeks) from initial presentation to IVF cycle start. Most Middle East nations do not maintain a comprehensive IVF database, and there is no independent agency to collect transnational data on IVF clinics. Our pilot study demonstrates that IVF programs in the Middle East could contribute voluntarily to collaborative network efforts to share clinical data, improve quality of care, and increase patient access to reproductive services in the region.

Background: A number of disputes have arisen in recent years over the status of non-transferred embryos cryopreserved during in vitro fertilisation. One such case is that of Natallie Evans who in April 2007 lost her final attempt to prevent the destruction of embryos created with the sperm of her former partner. Ms Evans had been rendered infertile by cancer treatment, and the embryos represented her only chance of having genetically related children.

Discussion: Arguments over stored embryos often conflate different concepts of parenthood. The effects of 'forcing' genetic parenthood on a man are mistakenly presented as being analogous with forcing women to bear children. Likewise, there is a tendency to assume that genetic parenthood necessarily involves legal, financial and psychological implications. Men (or women) who object to becoming parents should be encouraged to specify which aspects of parenthood they regard as being harmful. While the financial or physical burdens of forced parenthood involve objective harms, the putative psychological harms of enforced genetic parenthood are subjective, and this distinction should be recognised. Popular beliefs about genetic parenthood perpetuate the kinds of subjective concerns expressed by Ms Evans' partner, but the concept of genetic parenthood itself may come under pressure in the face of future technological developments.

Summary: Historical legal requirements obliging men to provide for their genetic offspring still pervade in the law. These perceptions are becoming outmoded in context of rapidly-moving reproductive technologies. To avoid disputes greater flexibility is required. The economic and legal components of parenthood should be negotiable in cases where disputes arise, and should not be assumed to flow inexorably from genetic paternity. To reduce the chances of disputes arising, consent protocols for cryopreservation of non-transferred embryos should be refined. Couples should address the possibility of divorce or the breakup of their relationships, and should be made aware that embryos can be destroyed at the behest of either party in these circumstances.

Background: To determine whether estradiol-to-progesterone (E2/P) ratios at the time of embryo transfer (ET) have an effect on implantation and pregnancy in IVF cycles.

Methods: 239 women consecutively treated by IVF or ICSI were retrospectively analyzed and early luteal serum E2 and P were measured on the day of ET. Transfer occurred after a variable in vitro culture period ranging from 4-7 days after ovulation induction (OI). Following ET, serum E2/P ratios were calculated for clinical pregnancies, preclinical abortions and non-conception cycles.

Results: Receiver-operator curve analysis demonstrated that the E2/P ratio could differentiate between clinical pregnancies and non-pregnant cycles (area under the curve on OI +4 days = 0.70; 95% CI = 0.60-0.80; p = 0.003, on OI +5 days = 0.76; 95% CI = 0.64-0.88; p = 0.001, OI +7 days = 0.85; 95% CI = 0.75-0.96; p < 0.0001).

Conclusion: These retrospective data may hold prognostic value regarding endometrial receptivity as reflected by E2/P measurements and may help improve IVF treatment outcome. Further prospective studies should be undertaken to confirm these obersveration.

The publication of a report in Nature in 2004 by the Tilly group suggesting that mouse ovaries are capable of generating oocytes de novo post-natally, has sparked interest in a problem long thought to have been resolved from classical studies in a variety of mammalian species. Within a nearly two year time period, laboratories around the world have taken up the challenge to dogma raised by this initial report, either to test this concept in an experimental basic science setting or give direction to clinical applications that could result, were the original premises of this work in the mouse valid for extrapolation to humans. This review provides a status report for this promising area of research, (1) to summarize recent findings in the literature with respect to the validity of the original hypothesis proffered by the Tilly group, and, (2) to gauge the potential utility of ovarian stem cells as a treatment for certain forms of human infertility.

Background: Intracytoplasmic sperm injection (ICSI) is a component of infertility treatment often employed when conventional in vitro fertilization is unlikely to be successful. Despite good clinical results with ICSI, the procedure is typically associated with degeneration of a significant percentage (approximately 10%) of the treated oocytes. The cause of this degeneration remains unclear. Speculation that damage caused by oocyte compression during the injection procedure may be responsible has led to the development of a novel technique known as laser-assisted ICSI. This procedure involves drilling a small hole through the zona pellucida with a laser prior to sperm injection. Preliminary studies have suggested that laser-assisted ICSI may dramatically reduce oocyte degeneration rates. The objective of this study was to examine whether the reported benefits of laser-assisted ICSI could be verified on a larger, less-selected group of patients.

Methods: Oocytes retrieved from 59 patients scheduled for ICSI were randomly divided into equal treatment and control groups. Oocytes in the treatment group were inseminated by laser-assisted ICSI, while oocytes in the control group were inseminated by conventional ICSI. Outcome variables (oocyte fertilization and degeneration, embryo cell numbers and fragmentation on days 2 and 3, and compaction and blastocyst formation rates) were compared between treatment and control groups by paired-sample t-test. Subgroup analysis was performed according to zona pellucida and oolemma breakage patterns.

Results: No significant differences between treatment and control groups were observed for any of the measured outcome variables. However, fragile zonae pellucidae were associated with significantly poorer embryo quality, and fragile oolemmas that broke easily upon insertion of the injection needle were associated with a significantly higher oocyte degeneration rate. Nevertheless, there were also no between-treatment differences in clinical outcomes within these patient subpopulations.

Conclusion: Contrary to previous reports based on smaller sample sizes, the results of this study suggest that there is no benefit of laser-assisted ICSI, either for the general population of ICSI patients, or for patients prone to zona pellucida or oolemma fragility.

Background: Progesterone receptor act as ligand-inducible transcription factor in the respective target cells by binding to specific progesterone response elements in the promoter of the target genes. However, despite the lack of the classical progesterone response elements on matrix-metalloproteinase-2 promoter, progesterone has been shown to decrease the activity of this promoter.

Presentation of the hypothesis: It has recently been suggested that in addition to interacting with their classical co-activators and co-repressors, progesterone receptor are capable of binding to several transcription factors. By interacting with other classes of transcription factors, progesterone receptor is capable of transcriptional activation through the transcription factors cognate DNA binding site.

Testing the hypothesis: Exploring transcription factors and transcription binding sites, interacting with the progesterone receptor in modulation of the matrix-metalloproteinase promoter.

Implications of the hypothesis: Identification of additional endogenous progesterone target genes makes it possible to further explore the signaling mechanisms by which the hormone regulates biological actions. Furthermore, the concepts of ligand-driven conformational diversity and selective tissue actions can be exploited in the future for drug development which selectively regulate orphan receptors from the nuclear receptor family.

Recent studies have demonstrated that the endogenous cannabinoids are important modulators of fertility in mammals. In particular, a role of the endocannabinoid system in early stages of embryo development, oviductal transport of embryos, pregnancy maintenance and labour has been demonstrated in rodents and/or in humans. In the present paper, we report the analysis of FAAH activity and protein content in the mouse uterus as a function of the natural oestrus cycle stages. Variations of FAAH activity are discussed in relationship to changes in sex steroid levels and to the possible action of AEA on remodelling of uterine tissues.

Background: Laboratory animals are commonly used for evaluating the physiological properties of the mammalian ovarian follicle and the enclosed oocyte. The use of different species to determine the morphological relationship between the follicle and oocyte has led to a recognizable pattern of follicular stages, but differences in follicle size, oocyte diameter and granulosa cell proliferation are not consistent across the different species. In an effort to better understand how these differences are expressed across multiple species, this investigation evaluates oocyte and follicle diameters and granulosa cell proliferation in the mouse, hamster, pig, and human.

Methods: Histological sections of ovaries from the mouse, hamster, pig, and human were used to calculate the diameter of the oocyte and follicle and the number of granulosa cells present at pre-determined stages of follicular development. A statistical analysis of these data was performed to determine the relationship of follicular growth and development within and between the species tested.

Results: These data have revealed that the relationships of the features listed are tightly regulated within each species, but they vary between the species studied.

Conclusion: This information may be useful for comparative studies conducted in different animal models and the human.

About 30-40% of male infertility is due to unknown reasons. Genetic contributions to the disruption of spermatogenesis are suggested and amongst the genetic factors studied, Y chromosome microdeletions represent the most common one. Screening for microdeletions in AZFa, b and c region of Y chromosome showed a big variation among different studies. The purpose of this study was to investigate the prevalence of such deletions in Saudi men. A total of 257 patients with idiopathic oligo- or azoospermia were screened for Y chromosome microdeletions by 19 markers in AZF region. Ten (3.9%) patients had chromosomal rearrangements, six of them showed sex chromosome abnormalities and four patients had apparently balanced autosomal rearrangements. Eight of the remaining 247 patients (3.2%) with a normal karyotype and no known causes of impaired spermatogenesis had Y chromosome microdeletions. Among these, six patients had deletions in AZFc region, one case had a deletion in AZFb and another had both AZFa and AZFc deletions.In conclusion, our study shows that Y chromosome microdeletions are low in our population. We also report for the first time a case with unique point deletions of AZFa and AZFc regions. The lower frequency of deletions in our study suggest that other genetic, epigenetic, nutritional and local factors may be responsible for idiopathic oligo- or azoospermia in the Saudi population.

Background: The relation between vascular endothelial growth factor (VEGF) and early luteal function has rarely been proven in humans. The purpose of this study was to define the relation between follicular fluid concentrations of VEGF (FF VEGF) and early luteal function at the preimplantation stage during assisted reproductive technology (ART) cycles.

Methods: 71 women were divided into two groups, based on reproductive outcome: women who became pregnant after embryo transfer (ET) (n = 18, Group A) and non-pregnant women (n = 53, Group B). Serum progesterone (Se P) and inhibin A on ET day, and FF VEGF levels were measured in all women. Data were expressed as mean +/- standard deviation. Statistical analysis was performed using Excel Office 98 for Student's t-test, linear regression test and chi-square test. A p value of < 0.05 was considered statistically significant.

Results: The groups were comparable for age, ovarian reserve, number and quality of the oocytes retrieved and of the embryos obtained and transferred. FF VEGF levels were increased (4235 +/- 1433 vs 3432 +/- 1231 pg/ml), while Se P and inhibin A levels were significantly reduced (83.1 +/- 34.1 vs 112.0 +/- 58.8 ng/ml and 397.4 +/- 223 vs 533.5 +/- 283 pg/ml, respectively) in the non-pregnant group and were negatively correlated with FF VEGF (r = -0.482, p < 0.05; r = -0.468, p < 0.05) only in pregnant women.

Conclusion: Much has to be learned about the regulation and role of VEGF during the early luteal phase. We advance the hypothesis that the existence of a negative correlation between FF VEGF/Se P and FF VEGF/inhibin A in pregnant women might indicate the existence of a normal VEGF-mediated paracrine response when Se P and inhibin A levels are decreased. Excess production of FF VEGF and the absence of a correlation between FF VEGF/Se P and FF VEGF/inhibin A in non-pregnant women may be a paracrine reaction to immature luteal vasculature, resulting in luteal dysfunction.