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Use of reproductive technology to estimate variances and predict effects of gene interactions.

Advanced reproductive techniques are creating the large numbers of close relatives needed to study gene interactions. Identical triplets, a set of 26 full sisters, a family of 4215 three-quarter sisters (same sire and maternal grandsire), a family of 76,698 half sisters, and 1.6 million granddaughters of Round Oak Rag Apple Elevation now have lactation records. Similarity of closest relatives might be explained by similar nonadditive as well as additive genetic merit. The 23,015 families of full sisters with mean family size of 3 provide nearly as much information about dominance variation as do the 55,779 families of three-quarter sisters with mean family size of 13; the 79 families of clones provide little information by comparison. Hypothetically, REML analysis of all US Holstein data could provide estimates of dominance and additive x additive variance with standard errors approximately 1% of phenotypic variance, but estimates of any higher order interactions would have standard errors greater than 10%. The tilde-hat approximation proved to be incompatible with animal models but was used for sire-maternal grandsire analysis of 765,868 first lactation records. Dominance variance was estimated as 3.5% of phenotypic variance for milk and 3.3% for fat with standard error of 4.2%. With constant data set size, variances are estimated most precisely if family sizes equal 1 plus ratio of within-family to between-family variance. An animal model evaluation including dominance relationships for 581,670 animals was computed, but gene interactions from distant ancestor pairs were ignored. Mating advice and improved additive predictions, especially for clones, could be obtained by including dominance in models.

Animals↗

Association between Beckwith-Wiedemann syndrome and assisted reproductive technology: a case series of 19 patients.

OBJECTIVE: An association between assisted reproductive technique (ART) and specific imprinting mutations, such as Beckwith-Wiedemann syndrome (BWS), has recently been documented. Based on experiments in farm animals that demonstrated an association between alterations in culture media during ART and large offspring syndrome, we hypothesized that the culture media could be implicated as a common factor among the children with BWS conceived after ART. DESIGN: Retrospective case series. SETTING: Registry from Academic Medical Center. PATIENT(S): Nineteen children born after ART were identified within the registry. MAIN OUTCOME MEASURE(S): Demographics of patients, type of ART, culture media, IVF parameters. RESULT(S): Twelve of the 19 medical records from the reproductive endocrine centers were successfully obtained. Ten of 12 mothers of children with BWS had IVF, but no single, consistent culture media was used in this group. Half of the patients underwent IVF with intracytoplasmic sperm injection (ICSI; n = 5), whereas the other half had routine IVF. One child was conceived through clomiphene citrate (CC) stimulation and artificial insemination, whereas another patient conceived through gonadotropin stimulation with intrauterine insemination (IUI). The gonadotropin dosage and quantity of embryos transferred also varied significantly. The only consistent finding was that all 12 women received some type of ovarian stimulation medication. CONCLUSION(S): Large epidemiologic studies are needed to further study the association between BWS and ART.

Adolescent↗

[Child and families in the era of reproduction technology--new questions within the scope of child psychiatric treatment].

In the last years the number of children born after assisted human reproduction has increased significantly. These technologies have created new challenges for the families as well as for the professionals involved. This article provides an overview of families after in-vitro-fertilisation, intracytoplasmatic sperm injection and donor insemination. The impact of the specific family composition after DI is described in detail. Two case histories indicate that these families may be confronted with psychiatric and child-development issues. Therefore it is helpful to understand the specific issues of these families. Prospective studies will play an important role in order to understand the quality of parent-child-relationship as well as psychological coping strategies, especially in times of crisis.

Adaptation, Psychological↗

Sperm deoxyribonucleic acid fragmentation as a prognostic indicator of assisted reproductive technology outcome.

OBJECTIVE: To examine sperm DNA fragmentation in semen used for assisted reproduction procedures to establish this factor's prognostic role in fertilization rate, embryo development, pregnancy rate, and outcome. DESIGN: Prospective study. SETTING: Department of Medicine and Biology of Reproduction of the Edouard Herriot Hospital in Lyon, France. PATIENT(S): 322 couples, divided into 88 cycles of in vitro fertilization (IVF) or 234 cycles of intracytoplasmic sperm injection (ICSI). INTERVENTION(S): Sperm DNA fragmentation was detected in sperm obtained 2 to 5 months before the ART procedure. MAIN OUTCOME MEASURE(S): Sperm DNA fragmentation was measured with the terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling (TUNEL) technique. RESULT(S): There was a negative statistical correlation between the rate of fragmentation and the semen characteristics. A statistically significant negative relationship was found for sperm DNA fragmentation and fertilization when ICSI and IVF were compared. With ICSI, a statistically significant negative relationship was found between fertilization rate and percentage of sperm DNA fragmentation (DNA fragmentation index, or DFI). The risk of nontransfer due to blocked embryo development increased when the DFI exceeded 15% (18.2% for ICSI vs 4.2% for IVF) with an odds ratio of 5.05. The miscarriage risk increased fourfold when the DFI exceeded 15% (37.5% for ICSI vs 8.8% for IVF). CONCLUSION(S): Sperm DNA fragmentation measured 2 to 5 months before the assisted reproduction procedure was a prognostic indicator of the fertilization, pregnancy, and miscarriage rates and the pregnancy outcome.

Adult↗

Role of embryo quality in predicting early pregnancy loss following assisted reproductive technology.

Early pregnancy loss (EPL) significantly reduces the initial success rate of assisted reproduction treatments and increases the psychological burden on the patient. The aim of the current study was to investigate the association between embryo quality and EPL in IVF. A retrospective study of 1471 women undergoing IVF between July 2000 and October 2004 was performed. Multivariate logistic regression models evaluated the effect on EPL of the woman's age, type and cause of infertility, endometrial thickness on the day of oocyte retrieval, performance of intracytoplasmic sperm injection, number of transferred embryos, embryo quality as assessed by the number of blastomeres in the leading transferred embryo at day 3, and the percentage of fragmentation. The 2902 oocyte retrieval-embryo transfer cycles resulted in 816 pregnancies (28.1%; 705 women) constituting the study cohort. Of these, 259 pregnancies (31.7%) ended in EPL and 557 (68.3%) in ongoing pregnancies. EPL risk was significantly associated with advanced (>35 years) maternal age (OR=1.53; 95% CI 1.12-2.09) and five or fewer blastomeres in the leading embryo transferred at day 3 (OR=1.82; 95% CI 1.16-2.85). In conclusion, the quality of transferred embryos, as assessed by the total number of blastomeres in the leading transferred embryo, and maternal age are predictors of EPL.

Abortion, Spontaneous↗

Children by choice: reproductive technologies and the boundaries of personal autonomy.

Unlike other countries that regulate assisted reproduction, the US has largely left this field to the domain of professional self-regulation and market preferences. The reason lies both in the confused jurisprudence of reproductive liberty and the paralysing effect of the abortion debate on US politics. The debate surrounding cloning, however, has galvanized both activists and the government to revisit the question of regulation, and recent cases in the US Supreme Court suggest that if the political will to regulate this field is found, governmental authority to intervene in areas such as pre-implantation diagnosis, gamete donation and surrogacy might well be upheld, even in the face of constitutional challenges.

Abortion, Induced↗

Assisted reproductive technology in Europe, 1997. Results generated from European registers by ESHRE. European IVF-Monitoring Programme (EIM), for the European Society of Human Reproduction and Embryology (ESHRE).

European results of assisted reproductive techniques from treatments initiated during 1997 are presented in this first ESHRE report. Data were collected from 18 European countries, usually from already-existing national registers. A total of 482 clinics from these 18 countries reported 203 893 cycles. In 10 countries with complete registration, 133215 cycles were performed in a population of 174 million, corresponding to 765 cycles per million inhabitants. After IVF and intracytoplasmic sperm injection (ICSI), the distribution of transfer of one, two, three and four or more embryos was 11.5, 35.9, 38.4 and 14.3% respectively. Huge differences existed between countries. For IVF, the clinical pregnancy rate per transfer was 26.1%, and the delivery rate per embryo transfer 20.9%. For ICSI, the corresponding rates were 26.4% and 21.5%. Singleton, twin, triplet and quadruplet delivery rates for IVF were 70.4, 25.8, 3.6 and 0.2% respectively, giving a total multiple delivery rate for IVF of 29.6%. After ICSI, the corresponding rates were 71.7, 25.2, 2.9 and 0.1%, amounting to a total multiple delivery rate of 28.2%. The range of triplet delivery rates after IVF range from 0.4% to 11.9% among countries.

Embryo Transfer↗

The regulation of assisted reproductive technology: a comparative study of permissive and prescriptive laws and policies.

A specific statute governing assisted reproduction is one way to regulate assisted reproduction. However, what type of statute is best suited to an area of medicine that is subject to rapid technological advances and also affects human rights and interests? What are the strengths and weaknesses of a permissive model of regulation compared to a prescriptive model of regulation? This article examines the Human Fertilisation and Embryology Act 1990 (UK) and the Infertility Treatment Act 1995 (Vic) in the context of eligibility for infertility treatment and the roles played by the United Kingdom Human Fertilisation Embryology Authority and the Victorian Infertility Treatment Authority.

Australia↗