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Absence of sperm sex chromosome aneuploidies in an X0/XYY man.

OBJECTIVE: To determine appropriate genetic counseling of patients with a mosaic karyotype who wished to undergo assisted reproduction technology. DESIGN: Case report. SETTING: A tertiary center for assisted reproduction technology. PATIENT(S): A male with a mosaic karyotype X0/XYY. INTERVENTION(S): Analysis of ejaculated spermatozoa by using fluorescence in situ hybridisation with probes directed against chromosomes X, Y, and 18. MAIN OUTCOME MEASURE(S): Degree of sex chromosome aneuploidies in spermatozoa. RESULT(S): Levels of sex chromosome aneuploidies in spermatozoa were normal. On the basis of these findings, the couple proceeded to assisted reproduction technology without preimplantation genetic diagnosis and conceived a healthy male baby. CONCLUSION(S): Sex chromosome mosaicism in men does not necessarily lead to high levels of abnormal spermatozoa. Sex chromosome aneuploidies may be eliminated in the testes through the selective degeneration of abnormal spermatogenic cells.

Adult↗

Gametes, law and modern preoccupations.

This article surveys a range of recent media stories about human gametes, pinning them to a series of wider preoccupations within late modern life. Three preoccupations are singled out: first, kinship and relational identity; secondly, Nature and globalization; and finally, sexual difference and equality. Each one of these preoccupations has been characterised as iconic; debates about them are said to crystallize who we are, especially our uncertainties, and what we will be in the future. By indexing these preoccupations to the stories about human gametes, the article aims to upset both the increasing attempts to present assisted reproduction technologies as 'familiar' (as Nature's 'helping hand', for example) and the recurring assumptions about this technology's alleged 'novelty' and 'anomaly'. The article concludes that treating reproduction technologies, and their regulation, as 'familiar' risks complacency: equally, assumptions about their 'novelty' narrows the search for effective explanatory tools and regulatory mechanisms. The upshot is that it might be best for us to view reproductive technologies as both less 'familiar' and less 'novel'.

Attitude to Health↗

Clinical outcomes among recipients of donated eggs: an analysis of the U.S. national experience, 1996-1998.

OBJECTIVE: To evaluate the role of recipient age on the outcome of donor egg cycles. DESIGN: Retrospective cohort study of aggregated national cycles of donor egg therapy that are collected by Society for Assisted Reproductive Technology and the Centers for Disease Control and Prevention. SETTING: Assisted reproductive technology centers in the United States that report their results to the Centers for Disease Control and Prevention by way of the Society for Assisted Reproductive Technology. PATIENT(S): Recipients of embryos (17,339 cycles) derived from donated eggs between 1996 and 1998. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rates of implantation, clinical intrauterine pregnancy, pregnancy loss, and delivery based on the age of the recipient. RESULT(S): Success of donor egg therapy was remarkably constant among recipients aged 25 years through those in their late forties. At higher ages, declining rates of implantation, clinical pregnancy, and delivery were seen, along with small increases of pregnancy loss. During the course of the 3 years studied, fewer embryos were transferred and higher rates of implantation were observed. CONCLUSION(S): The success of donor egg therapy is unaffected by recipient age up to the later 40s, after which they begin to decline. Although recipient age per se is likely to be the major cause of this effect, other factors may contribute to this observation.

Abortion, Spontaneous↗

Intracytoplasmic sperm injection pregnancy after low-dose human chorionic gonadotropin alone to support ovarian folliculogenesis.

OBJECTIVE: To prove that several days of low-dose hCG alone can be used to stimulate folliculogenesis, complete FSH-initiated follicle/oocyte maturation, and achieve pregnancy in assisted reproduction technology. DESIGN: Case report. SETTING: Reproductive endocrinology center at an academic institution. PATIENT(S): A 35-year-old female patient and her partner with male-related infertility. INTERVENTION(S): After an 8-day priming with hMG (225 IU/d), we administered low-dose hCG (200 IU/d) alone for 5 days in one GnRH-agonist suppressed patient until proper follicle development was obtained and intracytoplasmic sperm injection was performed. MAIN OUTCOME MEASURE(S): Daily serum levels of LH, FSH, hCG, E(2), P, and T; measurements of follicle number and size; oocytes retrieved and fertilized; pregnancy. RESULT(S): Although FSH levels rapidly declined after hMG discontinuation, E(2) and large follicles increased during hCG-only administration. Several good quality oocytes were retrieved and fertilized by intracytoplasmic sperm injection; three embryos were transferred and a twin pregnancy ensued. CONCLUSION(S): Replacement of FSH with low-dose hCG for several days in the late ovulation induction stages of assisted reproduction technology resulted in: [1] continued growth of large ovarian follicles and E(2); [2] an optimal preovulatory follicle pattern consisting of many large and few medium and small follicles; and [3] reproductively competent oocytes and pregnancy.

Adult↗

What is the most relevant standard of success in assisted reproduction? The singleton, term gestation, live birth rate per cycle initiated: the BESST endpoint for assisted reproduction.

Assisted reproduction programmes do not report success consistently. Rates vary with the definition used. Success must reflect delivery of healthy babies, and the burden of treatment to couples. We report the singleton, term gestation, live birth rate of a baby per assisted reproductive technology cycle initiated for a large IVF programme. We defined assisted reproductive technology cycles as those initiated with the intention of oocyte collection. We examined cycles conducted through Monash IVF in 2001. All women with positive pregnancy tests had first trimester ultrasonography. Obstetric outcomes were recorded. All babies had neonatal examinations conducted by paediatricians. A total of 644 positive pregnancy tests were recorded in 2600 cycles; 509 showed fetal heart motion. Of 448 deliveries, 328 were singleton and 120 were multiple. There were 290 singleton deliveries at term gestation. In 2001, a couple had an 11.1% chance of delivering a singleton, term gestation, live baby per assisted reproductive technology cycle begun. We suggest that delivery of a single, term gestation, live baby per cycle initiated is the most relevant standard of success. This statistic was 11.1% at Monash IVF. We encourage programmes to report this BESST (Birth Emphasizing a Successful Singleton at Term) outcome.

Adult↗

Effects of maternal age on oocyte developmental competence.

The widespread use of a variety of assisted reproductive technologies has removed many of the constraints that previously restricted mammalian reproduction to the period between onset of puberty and reproductive senescence. In vitro embryo production systems now allow oocytes from very young animals to undergo fertilization and form embryos capable of development to normal offspring, albeit at somewhat reduced efficiencies compared to oocytes from adult females. They also can overcome infertility associated with advanced age of animals and women. This review examines oocyte developmental competence as the limiting factor in applications of assisted reproductive technologies for both juvenile and aged females. Age of oocyte donor is a significant factor influencing developmental competence of the oocyte. Age-related abnormalities of oocytes include a) meiotic incompetence or inability to complete meiotic maturation resulting in oocytes incapable of fertilization; b) errors in meiosis that can be compatible with fertilization but lead to genetic abnormalities that compromise embryo viability; and c) cytoplasmic deficiencies that are expressed at several stages of development before or after fertilization. In general, oocytes from juvenile donors and the embryos derived therefrom appear less robust and may be less tolerant to suboptimal handling and in vitro culture conditions than are adult oocytes. Research to identify specific cytoplasmic deficiencies of juvenile oocytes may enable modifications of culture conditions to correct such deficiencies and thus enhance developmental competence. Use of oocytes from aged donors for assisted reproduction can have a variety of applications such as extending the reproductive life of individual old females whose offspring still have high commercial value, and conservation of genetic resources such as rare breeds of livestock and endangered species. In general, female fertility decreases with advancing age. Studies of women in oocyte donation programs have established reduced oocyte competence as the major cause of declining fertility with age, although inadequate endometrial function can also be a contributing factor. Most research has emphasized the importance of chromosomal abnormalities because of the well established increase in aneuploidy with increasing maternal age but little is known about the underlying cellular and molecular mechanisms. Research aimed at identifying the specific developmental deficiencies of oocytes from juvenile donors and abnormalities of oocytes from aged females will assist in overcoming present bottlenecks that limit the efficiency of assisted reproduction technologies. Such research will also be crucial to the development of new oocyte-based technologies for overcoming infertility and possibly subverting chromosomal abnormalities in women approaching menopause.

Animals↗

The geriatric gravida: multifetal pregnancy reduction, donor eggs, and aggressive infertility treatments.

OBJECTIVE: Recent technologic advances and societal acceptance have dramatically increased the use of donor eggs for infertile couples who require assisted reproductive technologies. Now many "older" couples can access assisted reproductive technologies to achieve pregnancies. We sought to evaluate the changing pattern of patients referred for multifetal pregnancy reduction as a result of donor eggs and age factors in aggressive infertility treatment. STUDY DESIGN: Patients undergoing multifetal pregnancy reduction from 1986 to 1996 were included and categorized by year groupings, age, and the use of donor eggs. RESULTS: A total of 523 patients were referred for and underwent multifetal pregnancy reduction. Before 1994, only 4 of 226 (1.8%) had received donor eggs, whereas in 1994 to 1996, 29 of 297 (9.8%) had received donor eggs (chi 2 = 12.6, p < 0.001). Eight of 9 patients aged > or = 45 years undergoing multifetal pregnancy reduction received donor eggs. There were no patients aged > or = 45 years before 1994 but 9 in 1994 to 1996. Four of 9 patients aged > or = 45 years with multifetal pregnancies chose reduction to singleton gestation. The proportions of patients aged > or = 40 years have increased from 0% to 11% in the last 8 years. CONCLUSIONS: The availability of donor eggs has dramatically increased the use of assisted reproductive technologies and subsequent use of multifetal pregnancy reduction in older patients. Older patients are more inclined to want reduction to singleton gestation; they cite parental demands, financial issues, and their ability to parent in their 60s and 70s as reasons for reduction to singleton gestation.

Adult↗

Increased risk of placenta previa in pregnancies following IVF/ICSI; a comparison of ART and non-ART pregnancies in the same mother.

BACKGROUND: The risk of placenta previa may be increased in pregnancies conceived by assisted reproduction technology (ART). Whether the increased risk is due to factors related to the reproductive technology, or associated with maternal factors, is not known. METHODS: In a nationwide population-based study, we included 845,384 pregnancies reported to the Medical Birth Registry of Norway between 1988 and 2002 and compared the risk of placenta previa in 7568 pregnancies conceived after assisted fertilization, with the risk in naturally conceived pregnancies. To study the influence of ART more directly, we compared the risk of placenta previa between consecutive pregnancies among 1349 women who had conceived both naturally and after assisted fertilization. Odds ratios (OR), adjusted for maternal age, parity, previous Caesarean section and time interval between pregnancies were estimated using logistic regression. RESULTS: There was a six-fold higher risk of placenta previa in singleton pregnancies conceived by assisted fertilization compared with naturally conceived pregnancies [adjusted OR 5.6, 95% confidence interval (CI) 4.4-7.0]. Among mothers who had conceived both naturally and after assisted fertilization, the risk of placenta previa was nearly three-fold higher in the pregnancy following assisted fertilization (adjusted OR 2.9, 95% CI 1.4-6.1), compared with that in the naturally conceived pregnancy. CONCLUSIONS: The use of ART is associated with an increased risk of placenta previa. Our findings suggest that the increased risk may be caused by factors related to the reproductive technology.

Adult↗

Assisted reproduction versus spontaneous conception: a comparison of the developmental outcomes in twins.

The use of assisted reproductive technology is increasing rapidly. Research, although sparse, has resulted in inconsistent findings as to the developmental prognosis for infants conceived by assisted reproductive techniques such as in vitro fertilization and the use of fertility drugs. In the present study, the authors compared twins who were spontaneously conceived with those who were conceived through assisted reproductive technology. The authors found differences in birth weight and gestational age. Infants conceived by assisted reproductive technology fared worse than did those who were spontaneously conceived. The authors found no differences between the groups in mental development at 24 months of age, but they found evidence of differences in physical development. Implications of the findings are discussed.

Adult↗

Factors affecting commercial application of embryo technologies in dairy cattle in Europe--a modelling approach.

Reproductive techniques have a major impact on the structure of breeding programmes, the rate of genetic gain and dissemination of genetic gain in populations. This manuscript reviews the impact of reproductive technologies on the underlying components of genetic gain and inbreeding with special reference to the role of female reproductive technology. Evaluation of alternative breeding schemes should be based on genetic gain while constraining inbreeding. Optimum breeding schemes can be characterised by: decreased importance of sib information; increased accuracy at the expense of intensity; and a factorial mating strategy. If large-scale embryo cloning becomes feasible, this will have a small impact on the rate of genetic gain but will have a large impact on the structure of breeding programmes.

Animals↗

New technology and new challenges for assisted reproduction.

As assisted reproduction technology advances, more types of procedures are becoming available, bringing more success at solving many types of infertility. In vitro fertilization has become simpler and less invasive, with success rates as high as 30% per cycle. Intracytoplasmic sperm injection has solved many types of male infertility. This article explains in vitro fertilization technology and discusses such ethical issues as embryo ownership, multiple births, and embryo genetic testing.

Adult↗

Recent advances in reproductive genetic technologies.

New possibilities for the diagnosis and treatment of reproductive and genetic disorders are becoming available as a result of a series of recent technical advances. Intracytoplasmic sperm injection (ICSI) allows treatment of numerous infertile men whose sperm cannot penetrate the egg to initiate fertilization. Molecular genetic testing provides clients of reproductive age with additional information that permits prevention of genetic diseases such as fragile X syndrome, the leading cause of inherited mental retardation. Preimplantation genetic testing (PGT) offers couples who carry genetic disorders the prospect of having children with a greatly decreased risk of initiating a pregnancy involving an affected individual. Flow-cytometric sperm separation offers a new, effective approach for prevention of X-linked genetic disorders. Two major causes of recurrent pregnancy loss (RPL) involve recurrent trisomies and immunological disorders. Of the latter, 70% of studied populations of patients can attain live births with simple treatment protocols. Maternal serum assays involving multiple markers reduce both false positives and false negatives in detection of trisomies. Despite these advances in research, many safe and effective methods of diagnosis and treatment remain under-utilized in the clinical arena.

Abortion, Habitual↗

Triplets: outcomes of expectant management versus multifetal reduction for 127 pregnancies.

OBJECTIVE: Our purpose was to compare outcomes of women with triplet gestations conceived via assisted reproductive technology who chose expectant management or multifetal pregnancy reduction. STUDY DESIGN: We performed a retrospective review of all women who initiated assisted reproductive technology cycles from August 1995 through July 1997 with ultrasonographic documentation of triplets exhibiting fetal heart tones at 9 weeks of gestation (N = 127). Patients were then uniformly referred to a maternal-fetal medicine specialist and to 3 centers offering multifetal pregnancy reduction. RESULTS: Thirty-six percent of patients (46/127) chose multifetal pregnancy reduction with 95% undergoing reduction to twins. In the expectant management group, 13.6% of pregnancies were reduced spontaneously after 9 weeks of gestation. The "take home" infant per delivery rates for the multifetal pregnancy reduction and expectant management groups were 87% and 90.1%, respectively (P =.66). The mean gestational ages at delivery (+/-SE) for the multifetal pregnancy reduction and expectant management groups were 33.25 +/- 1. 03 weeks and 32.04 +/- 0.58 weeks (P =.23), and the mean birth weights of infants delivered at >24 weeks of gestation were 2226 +/- 79 and 1796 +/- 44, respectively (P <.0001). There were no significant differences in perinatal mortality, gestational age at delivery, or "take home" infant per delivery rates between these groups. CONCLUSIONS: These data suggest that multifetal pregnancy reduction does not have a significant impact on the probability of live birth or on gestational age at delivery for women with triplets conceived with assisted reproductive technology.

Abortion, Spontaneous↗

Luteal phase support.

OBJECTIVE: To develop a consensus regarding the need for luteal phase support during assisted reproductive technology (ART), and to establish the optimal compound and route of administration for this purpose. DESIGN: Review of the published literature on luteal phase support. PATIENT(S): Women undergoing assisted reproductive technologies. INTERVENTION(S): Progesterone was administered orally, vaginally, or by intramuscular (i.m.) injection to supplement the luteal phase after assisted reproductive technology (ART). MAIN OUTCOME MEASURE(S): Pregnancy following ART. RESULT(S); Gonadotropin releasing hormone (GnRH)-agonist protocols necessitate the use of luteal phase support. Progesterone and human chorionic gonadotrophin (hCG) have both been used for this purpose, with comparable outcomes. Progesterone is the product of choice, however, as it is associated with a lower incidence of ovarian hyperstimulation syndrome (OHSS). Its use is indicated up to the serum pregnancy test. Oral, i.m., and vaginal progesterone preparations are available. Intramuscular and vaginal preparations lead to comparable rates of implantation and clinical pregnancy, despite higher serum progesterone levels after i.m. injection. Oral formulations are inferior products for luteal support. Although widely used, i.m. progesterone is uncomfortable and inconvenient for patients. By contrast, the vaginal progesterone gel (Crinone 8%) is more convenient and easier to use. CONCLUSION(S): Progesterone support of the luteal phase in in vitro fertilization (IVF) cycles is indicated, though support beyond the serum pregnancy test may not be needed. The pregnancy rates after vaginal and i.m. progesterone support are comparable, despite higher serum levels after i.m. injection. Patients prefer the vaginal progesterone gel.

Administration, Intravaginal↗

Progress with oocyte cryopreservation.

PURPOSE OF REVIEW: This article reviews human oocyte cryopreservation, one of the most stimulating challenges of assisted reproduction technology. Since the first steps in assisted reproduction technology, researchers have pursued this goal, to greatly improve the management of infertility treatments. This present review depicts the present state of research and clinical applications of this methodology. RECENT FINDINGS: Recent literature focuses on the possible mechanisms of oocyte damage caused by temperature and cryoprotectant injury and forecasts possible technological solutions. Several papers illustrate encouraging results in the increasing clinical application of this procedure. SUMMARY: Findings give support to several indications of human female gamete cryostorage. Oocyte cryopreservation might replace embryo freezing. Egg freezing offers an alternative to women at risk of losing their reproductive function, caused by antineoplastic treatments, endometriosis, ovarian surgery or genetic premature ovarian failure. In addition, oocyte storage may contribute to an increase in in-vitro fertilization flexibility. Despite the early disappointing results, recent technical modifications have improved the clinical efficiency greatly, with the birth of several healthy children.

Cell Survival↗

Medical and economic effects of twin gestations.

OBJECTIVE: To determine the incidence and trends of twinning in the United States and to review the medical and economic effects of twin versus singleton gestations. METHODS: Pertinent and recent studies on twin gestations were obtained through a MEDLINE database search of the English language between December 1987 and December 1999. Data from the 1995-1996 National Center for Health Statistics were also used to compare gestational age at delivery, fetal growth restriction, and perinatal mortality for twin and singleton gestations. Studies that have evaluated perinatal risks in relation to advanced reproductive technology also were reviewed and summarized. The economic implications of twinning from a societal perspective and infant quality of life issues of twins compared with singleton gestations are reviewed. RESULTS: Due to delayed childbearing and increased use of reproductive technologies, the incidence of twin gestations in the United States has been increasing. Twin pregnancies have a higher risk of complications, including pregnancy-induced hypertension, anemia, antepartum and postpartum hemorrhage, and maternal mortality. In addition, twin infants are more likely to deliver preterm, have low birth weight and greater perinatal mortality rates. These outcomes influence health care costs and quality of life for both parents and children. CONCLUSIONS: Women carrying twin fetuses are at increased risk for perinatal and obstetric complications. The increased perinatal risks that accompany twin fetuses may be partly due to the increasing use of advanced reproductive technologies. The economic burdens, as well as the potential for decreased quality of life among twins, needs careful evaluation.

Economics↗

Heterotopic pregnancy: two cases and a comparative review.

OBJECTIVE: To analyze the incidence, diagnostic, and therapeutic management of heterotopic pregnancy by comparing a review for the 1971-1993 period with the one carried out in the present study (1994-2004). DESIGN: Review of the literature. SETTING: University teaching assisted reproductive technology (ART) center. PATIENT(S): Two case reports included in a comparative review of the literature on heterotopic pregnancy. INTERVENTION(S): Review of the published literature from January 1994 to December 2004 was performed by means of MEDLINE database. Medical subject heading words used were: heterotopic pregnancy, assisted reproductive technology, and ectopic pregnancy. A comparison with a previously reported review, including cases from 1971 to 1993. MAIN OUTCOME MEASURE(S): Comparative study of the diagnosis and treatment of ectopic pregnancy. RESULT(S): During the 1971-1993 period the definitive diagnosis of heterotopic pregnancy was performed by laparoscopy or laparotomy in 59% of cases. This proportion increased to 74% from 1994 to 2004. Likewise, the percentage of cases in which an early diagnosis was possible (performed before the ninth week of pregnancy) did not vary in any of the time periods evaluated (71% vs. 74%). CONCLUSION(S): Despite the increased medical knowledge and use of improved reproductive technologies, heterotopic pregnancy still remains a diagnostic and therapeutic challenge to practitioners.

Adult↗

Infertility treatment and informed consent: current practices of reproductive endocrinologists.

OBJECTIVE: To determine current practice patterns of obtaining informed consent for infertility treatment by reproductive endocrinologists and to assess changes in response to reports of an association between ovulation induction and ovarian cancer. METHODS: Board-certified reproductive endocrinologists (n = 575) were surveyed by mail regarding how they informed patients and obtained consent for infertility treatments and how their practices had been influenced by studies suggesting a link between ovulation induction and ovarian cancer. Data were analyzed using chi2 and logistic regression analyses. RESULTS: The return rate was 62.1% (357 of 575 surveys). Most respondents (92%) used discussions with physicians to inform their patients of risks and benefits of all infertility treatments. Additional means, such as audiovisual aids, were used significantly more often for assisted reproductive technologies (including intracytoplasmic sperm injection and use of donated eggs) than for less invasive therapies (31-43% versus 4-11%, P < .001). Most physicians (46-66%) used verbal consent alone for hysterosalpingogram, intrauterine insemination, and ovulation induction. Formal written consent was used significantly more often for the various assisted reproductive technologies than for hysterosalpingogram, intrauterine insemination, or ovulation induction (94-95% versus 26-44%). Although most physicians (70%) did not believe that ovulation induction increases the risk of ovarian cancer, 83% addressed this risk when obtaining consent and 47% reported changing their practices since an association was reported. Common changes included limiting length of treatment and addressing ovarian cancer risk. CONCLUSION: Current practice patterns of obtaining informed consent for various infertility treatments by board-certified reproductive endocrinologists show, as expected, that informed consent is more rigorous for assisted reproductive technologies. Although most surveyed did not believe that ovulation induction increases risk of ovarian cancer, the majority of physicians addressed that risk when obtaining consent and nearly half changed their practices on the basis of a possible association.

Data Collection↗