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Iatrogenic multiple pregnancy. Higher risk than a spontaneous one?

OBJECTIVE: To determine if spontaneous and induced multiple pregnancies have similar outcomes. STUDY DESIGN: We compared the results of antepartum and intrapartum surveillance and fetal outcome in spontaneous multiple gestations (group A) with induced multiple gestations (group B) at Albert Szent-Györgyi Medical University, Szeged, Hungary, in a six-year period. RESULTS: Between January 1, 1991, and December 31, 1996, there were 13,131 births; the number of multiple pregnancies was 307 (2.34%). There were 232 spontaneous and 48 induced twin pregnancies, 8 spontaneous and 16 induced triplet pregnancies, and 3 quadruplet pregnancies, all induced. Higher incidences of gestational diabetes and cervical insufficiency were found in group B. The incidences of prematurity in the induced and spontaneous groups were similar. The incidences of low birth weight and perinatal mortality were higher in induced triplet pregnancies than in spontaneous ones. Fetal outcome, with respect to Apgar score and umbilical cord blood pH, was much poorer in both induced groups. CONCLUSION: Iatrogenic multiple pregnancy following ovulation induction or assisted operative reproductive techniques may increase the incidence of pathologic events in the antepartum, intrapartum or postpartum period. Careful counseling before assisted reproductive techniques is of paramount importance.

Adult↗

Successful pregnancy following zygote intrafallopian transfer for congenital cervical hypoplasia.

BACKGROUND: Congenital cervical atresia and hypoplasia are rare abnormalities that generally require reconstructive or extirpative procedures to relieve outflow tract obstruction. Infertility is a common sequel, and only four previous pregnancies have been reported. In selected cases, zygote intrafallopian transfer (ZIFT) or other assisted reproductive techniques may offer alternatives for conception. CASE: A 21-year-old amenorrheic woman experienced a spontaneous gush of vaginal bleeding following an 11-year history of cyclic lower abdominal pain. Regular but prolonged and painful menses ensued. After another 8 years of primary infertility, transcervical and transfundal hysteroscopy demonstrated congenital cervical hypoplasia and a normal endometrial cavity. Conception was achieved during her third cycle of ZIFT. Delivery occurred by elective cesarean at 39 weeks for a persistent oblique fetal lie. CONCLUSION: A successful pregnancy was established following ZIFT in a woman with congenital cervical hypoplasia. The endometrial cavity was evaluated by a previously unreported technique, transfundal hysteroscopy. The use of appropriate surgical or assisted reproductive techniques in conjunction with individualized post-conception management may permit successful pregnancy and delivery in selected women with congenital cervical hypoplasia and atresia.

Adult↗

Ethical issues in modern biological technologies.

Today's biology-based technologies have emerged from a historical imperative and as an inevitable consequence of developments in modern biology beginning in the last half-century. They can be classified into almost 30 different areas, ranging from the use of gene therapy for human beings, enzyme engineering, stem cells and cloning, to marine biotechnology, bioinformatics, nanotechnology and biological warfare among many others. Many of them have major sociopolitico-economic, moral, ethical and legal implications. They include genetic engineering, gene therapy, tissue culture, stem cell work, the new DNA technologies, commercialization of traditional plant-based drug formulations, assisted reproduction techniques, cloning technologies, organ transplantation, bioinformatics, and biological weapons. Examples of the ethical implications of several of these items will be considered. They will be assessed with special reference to ethical implications in respect of assisted reproduction techniques, of worldwide importance today, particularly for a country such as India.

Biological Warfare↗

Women's reproductive health: monotheistic religious perspectives.

It is important to those who practice reproduction techniques to learn about the different religious attitudes related to reproductive health problems. Religion exerts an influence on civil authorities in the field of reproduction such as prevention or procreation and in issues such as abortion and infertility therapy. The Jewish attitude towards reproduction can be learned from the fact that the first commandment of God to Adam was be fruitful and multiply. Judaism allows the practice of all techniques of assisted reproduction when the oocyte and sperm originate from the wife and husband, respectively. All Rabbinical rulings permit the use of contraception for medical indications. Economic difficulties and inconveniences of raising children are not indications for birth control practice. According to Judaism abortion on demand is forbidden but it may be performed if the mother's life is in danger. The attitude toward reproductive practice is different among the different divisions of Christianity. The practice of assisted reproduction is not accepted by the Vatican, however, it may be practiced by Protestant, Anglican and other Denomination's. According to the Roman Catholic doctrine the primary purpose of marriage is procreation. The contraceptive act destroys the potential of producing new life by sexual intercourse and violates the purpose of marriage and, therefore, is a sin against nature. The Christian tradition views the embryo as a human being since conception and, therefore, abortion is strictly forbidden. According to Islam, the procedure of IVF and ET is acceptable, however, it can be preformed only if it involves the husband and the wife. It allows contraception practice only under some circumstances and only in some special cases abortion can be preformed. Religion, being concerned with affairs that are regarded as extraordinary and as having unique importance in life, is an intrinsic aspect of the culture of all societies, religious groups, however, still exert influence on the civil authorities in issues of reproduction such as contraception, procreation, abortion, and infertility therapy. They have been active in pressing their bioethical positions on the public arena in pluralistic societies. Developments in science and technology in reproduction raise new religious questions that do not always have clear answers. The role of theology in bioethics is foremost to clarify for the different religious communities the perceived attitudes toward these developments. Therefore, it is important to those who practice reproduction techniques to learn about the different religious attitudes related to reproductive health problems.

Abortion, Induced↗

Serum hormones for predicting pregnancy outcome after assisted reproductive technology.

Serum human chorionic gonadotrophin (HCG) in the second and third week after embryo transfer has been used for prediction of pregnancy outcome after assisted reproduction. There are few data on the clinical utility of HCG, progesterone and oestradiol, measured by contemporary immunoassay, in the fourth week after embryo transfer and later. Moreover, large inter-method differences have been described between automated immunoassays, making method-specific cut-off values mandatory. The main aim of this study was to determine assay-specific optimal cut-off values for serum HCG, progesterone and oestradiol for prediction of clinical pregnancy outcome in singleton pregnancies after assisted reproductive techniques, at days 11, 18 and 25 and at week 6 after embryo transfer. A retrospective study was performed on frozen serum samples of 67 singleton pregnancies after assisted reproduction techniques. HCG, oestradiol and progesterone were determined with the automated (random access) VIDAS immunoanalyser. Receiver operating characteristic curve analysis was performed to determine optimal cut-off values. Predictive values were calculated based on the prevalence of non-viable pregnancy after assisted reproduction. It was concluded that measurement of HCG by VIDAS at days 18 and 25, and at week 6 after embryo transfer yields high positive (70.5-100%) and negative (87.2-94.4%) predictive values for clinical pregnancy outcome.

Chorionic Gonadotropin↗

Collection, evaluation, and use of oocytes in equine assisted reproduction.

Assisted reproductive techniques have been developed to obtain pregnancies from subfertile mares and stallions and to salvage gametes after death. In recent years, these procedures have been used for clinical cases with repeated success. Although new developments occur, the basis for the success and future development of assisted reproductive techniques is our ability to collect and handle the equine oocyte successfully. This article focuses on important clinical aspects of oocyte collection and evaluation and briefly discusses the clinical use of assisted reproductive procedures in the horse.

Animals↗

Filiation is assisted reproduction: potential conflicts and legal implications.

Filiation, or a person's parentage, is one of the major components of someone's identity, often with important implications for that person's welfare in social and personal terms. Fertility specialists are enjoined to consider the welfare of the child, and this is a legal requirement in assisted reproduction techniques in the UK. This paper is in three parts, discussing some of the potential problems regarding filiation of the prospective child born of assisted reproduction techniques, in relation to the use of gametes and embryos. The first two parts concentrate on the status of children born as a result of treatment given posthumously, and on filiation problems associated with donation of gametes or embryos, and surrogacy. The third part compares British and French legislation with special regard to the welfare of the child, as well as underlining the common trends and principles enunciated in both legislations. This is particularly appropriate at a time when the European Society for Human Reproduction and Embryology is about to issue ethical guidelines in assisted reproduction, and when both the Council of Europe and the European Commission have commissioned studies on the implications of the assisted techniques, including those concerning status of the potential children.

Child Welfare↗

Triploid pregnancy after ICSI of frozen testicular spermatozoa into cryopreserved human oocytes: case report.

Although freezing oocytes is ethically more acceptable than cryopreservation of embryos, variable oocyte survival, fertilization rate and possible risk of increased ploidy after cryopreservation have precluded the widespread clinical application of oocyte cryopreservation in assisted reproduction techniques. We report a triploid pregnancy from intracytoplasmic sperm injection of recombinant FSH-stimulated frozen/thawed testicular spermatozoa into cryopreserved oocytes in a hormone replacement cycle. To our knowledge, this is the first report of a pregnancy where both gametes have been frozen. It illustrates the need for further research when applying new techniques in assisted reproduction.

Abortion, Missed↗

Reproductive biotechnologies for endangered mammalian species.

Assisted reproductive techniques (gamete cryopreservation, artificial insemination, embryo transfer, and in vitro fertilization) allow to propagate small fragmented populations of wild endangered species or domestic breeds. There are the best way for producing several offspring from selected genitors in order to avoid inbreeding depression. However, few mammalian species have been well studied for their reproductive biology whereas huge differences have been observed between these species. Furthermore, materials, methods and experimental designs have to be adapted for each case and each limiting factor (wildness, poor quantity of biological material, disparate locations). Genome resource banking is currently arising and the most applied reproductive biotechnology remains artificial insemination. Assisted reproductive techniques currently developed in domestic species (intracytoplasmic sperm injection, nuclear transfer) may offer new opportunities for the propagation of endangered species.

Animals↗

Advantage of combining magnetic cell separation with sperm preparation techniques.

The selection of vital, non-apoptotic spermatozoa is a prerequisite for achieving optimal conception rates in assisted reproductive techniques. Magnetic cell sorting using annexin-V microbeads can effectively separate apoptotic and non-apoptotic spermatozoa. The objective of the present study was to optimize the integration of magnetic cell sorting in standard sperm preparations and to correlate the effect of different sperm preparation procedures on apoptotic markers. Semen specimens collected from 15 healthy donors were prepared by either density gradient centrifugation or by one-step sperm wash technique separately and in combination with magnetic cell sorting. The preparation methods were evaluated by assessment of semen parameters (motility, viability and morphology) as well as markers of apoptosis (levels of active caspase-3, integrity of membrane mitochondrial potential and externalization of phosphatidylserine). The apoptotic markers were measured using fluorochrome dyes coupled with flow cytometry. The results showed that the combination of density gradient centrifugation and annexin-V magnetic cell sorting was superior to all other sperm preparation methods in terms of providing motile, viable and non-apoptotic spermatozoa. This study clearly shows the advantage of integrating magnetic cell sorting as a part of sperm preparation, which in turn may positively affect the success rates of assisted reproductive techniques.

Adult↗

[Management of twin births].

INTRODUCTION: The rate of multiple births has increased all over the world in the past decade. This is mainly due to the widespread use of infertility treatments and assisted reproductive techniques. Despite of improvements in obstetric and neonatal care, twin pregnancy still mean high risk both for the mothers and their babies. The management of twin delivery remains controversial. PATIENTS AND METHOD: Authors analyzed the data of all twin pregnancies at the Department of Obstetrics and Gynecology, University of Debrecen between January 2002 and December 2003. The data of 113 twin pregnancies were analyzed. Details of gestational age, presentation, birth weight discordance, mode of delivery were reviewed. RESULTS: From the 113 analyzed twin births, 27 pregnancies have been conceived after successful assisted reproductive technique. In 18 cases more than 500 grams of body weight difference was detected between the two babies at the time of delivery. The rate of preterm birth was 69%, and cesarean section was performed in 64% of preterm births compared to 68.6% in the matured delivery group. CONCLUSIONS: On the basis of recent data a large prospective, randomized trial is mandatory to determine the optimal management of twin deliveries.

Cesarean Section↗

Cost-effectiveness of infertility treatments: a cohort study.

OBJECTIVE: To determine the cost-effectiveness of infertility treatments. DESIGN: Retrospective cohort study. SETTING: Academic medical center infertility practice. PATIENT(S): All patients treated for infertility in a 1-year time span. INTERVENTION(S): Intrauterine inseminations, clomiphene citrate and IUI (CC-IUI), hMG and IUI (hMG-IUI), assisted reproductive techniques (ART), and neosalpingostomy by laparotomy. MAIN OUTCOME MEASURE(S): All medical charges and pregnancy outcomes associated with the treatments were obtained. Cost-effectiveness ratios defined as cost per delivery were determined for each procedure. The effects of a woman's age and the number of spermatozoa inseminated on cost-effectiveness of the procedures was also determined. RESULT(S): Intrauterine inseminations, CC-IUI, and hMG-IUI have a similar cost per delivery of between $7,800 and $10,300. All of these were more cost-effective than ART, which had a cost per delivery of $37,000. Assisted reproductive techniques in women with blocked fallopian tubes was more cost-effective than tubal surgery performed by laparotomy, which had a cost per delivery of $76,000. Increasing age in women and lower numbers of spermatozoa inseminated were factors leading to higher costs per delivery for IUI, CC-IUI, hMG-IUI, and ART. Use of donor oocytes reduced the cost per delivery of older women to the range seen in younger women with ART. CONCLUSION(S): Our analysis supports, in general, the use of IUI, CC-IUI, and hMG-IUI before ART in women with open fallopian tubes. For women with blocked fallopian tubes, IVF-ET appears to be the best treatment from a cost-effectiveness standpoint.

Clomiphene↗

ART in women 40 and over. Is the cost worth it?

OBJECTIVE: To determine the efficacy and cost of assisted reproductive techniques in older women (40 years or older) in comparison to younger women (less than 30 years old). STUDY DESIGN: Retrospective review of records from one university-based infertility practice. RESULTS: Women 40 years or older were significantly less likely to achieve pregnancy with human menopausal gonadotropin (hMG)/intrauterine insemination as compared to women under age 30. The older women were also significantly less likely to achieve pregnancy with in vitro fertilization (IVF). The use of donor oocytes resulted in the highest pregnancy rates in older women. Costs per cycle were similar, however, for both groups. CONCLUSION: Older women will consume an equal amount of medical resources per cycle in infertility treatment as compared to younger women (aged < 30 years). However, older women utilizing assisted reproductive techniques are four to five times less likely to achieve pregnancy than the younger group. This poor prognosis for success in older women adds significantly to the mean cost per pregnancy as compared to younger women. Donor oocytes may be the most cost-effective option for achieving pregnancy in older women.

Adult↗

Gynecological and reproductive issues for women in space: a review.

Women have been an integral part of United States space crews since the initial flight of Dr. Sally Ride in 1983, and a total of 40 women have been selected as U.S. astronauts. This article examines the reproductive and gynecological aspects of selecting, training, medically certifying, and flying women in space. Gynecological data from the astronaut selection cycles in 1991 to 1997 are reviewed. In addition, the reproductive implications of delaying childbearing for a career as an astronaut and the impact of new technology such as assisted reproductive techniques are examined. The reproductive outcomes of U.S. female astronauts after spaceflight are also presented. Because women have gained considerable operational experience on the Shuttle and Mir, the unique operational considerations for preflight certification, menstruation control and hygiene, contraception, and urination are discussed. Medical and surgical implications for women on long-duration missions to remote locations are still evolving, and enabling technologies for health care delivery are being developed. There has been considerable progress in the development of zero-gravity surgical techniques, including laparoscopy, thoracoscopy, and laparotomy. The concepts of prevention of illness, conversion of surgical conditions to medically treatable conditions, and surgical intervention for long-duration spaceflights are explored in detail. There currently are no operational gynecological or reproductive constraints for women that would preclude their successful participation in the exploration of our nearby solar system.

Adult↗

Determination of twin zygosity using a commercially available STR analysis of 15 unlinked loci and the gender-determining marker amelogenin--a preliminary report.

BACKGROUND: The aim of this preliminary study was to estimate the accuracy of the zygosity determination in twin pregnancies. METHODS: Seventy-three sets of twin pregnancies were enrolled in this study, including 48 sets of twins resulting from assisted reproductive techniques (ART) and 25 sets of spontaneously conceived twins. Determination of zygosity was made by PCR-amplified short tandem repeat (STR) analysis with a commercially available panel, comprising 15 autosomal, codominant, unlinked loci and the gender-determining marker, amelogenin. Monozygotic (MZ) twins were determined when all these unlinked loci and the gender-determining marker were identical. Chorionicity and placenta were examined after delivery of the newborns to check their relationships to the twin zygosities. RESULTS: Three of 48 (6.25%) sets of twins produced by ART and 18 of 25 (72%) sets of spontaneously conceived twins were MZ. Monozygosity could be evaluated based on 'like sex' in spontaneously conceived twins, because they had a greater incidence of MZs than those produced by artificial reproductive techniques. The MZ prediction rate was 78.6%, and the overestimated rate was 21.4% if the monochorionic like-sexed twins (LST) had a grossly single placenta. The underestimated rate of MZs was 26.7% when the dichorionic LST had apparently separate placentas. CONCLUSION: With the DNA-based 15 STR analysis amplified in a multiplex PCR, the determination of the zygosity in multifetal pregnancies is not only cost and time saving but also yields greater sensitivity and precision than conventional methods.

Adult↗

45,X/46,X,r(Y) karyotype transmitted by father to son after intracytoplasmic sperm injection for oligospermia. A case report.

BACKGROUND: The advent of assisted reproductive techniques, such as intracytoplasmic sperm injection (ICSI), has permitted conception and successful pregnancy for an increasing population of infertile men. Approximately 13.7% of infertile men with aspermia and 4.6% with oligospermia have a coexistent chromosome abnormality. Although the ICSI procedure appears safe thus far, early studies are in progress to evaluate outcomes of such pregnancies. For men whose infertility is linked to genetic conditions, it is an unprecedented challenge to predict the potential effects on their offspring. CASE: At 18 weeks' gestation, a 45,X/46,X,r(Y) karyotype was found on genetic amniocentesis performed for advanced maternal age. The pregnancy was achieved by ICSI using sperm from the husband, who was infertile due to severe oligospermia. Subsequently the same karyotype was found in the father. To our knowledge, this is the first reported case of familial transmission of ring Y chromosome. CONCLUSION: It is strongly recommended that ICSI and other new assisted reproductive techniques be preceded by genetic screening for male infertility as well as other indications warranted by the family history since traditional risk assessment may require revision and outcomes may be uncertain in some cases.

Adult↗

Serum insulin-like growth factor-I (IGF-I) and growth in children born after assisted reproduction.

CONTEXT: Concern has been raised about the safety of assisted reproduction techniques for the offspring. OBJECTIVES: The objective of the study was to investigate postnatal growth and growth factors in children born after intra-cytoplasmatic sperm injection (ICSI) and in vitro fertilization (IVF). DESIGN: The study had two cohorts: a population-based longitudinal infant cohort 0-36 months [236 ICSI, 173 IVF, 1530 naturally conceived (NC)], and a cross-sectional child cohort at 5 yr (68 ICSI, 67 IVF, 70 NC). INTERVENTION: Anthropometrical measurements were made at birth, 3, 18, 36 (infant cohort), and 60 months (child cohort), and blood samples were collected at 3 or 60 months. MAIN OUTCOME MEASURES: Serum IGF-I, IGFBP-3, height, weight, head and abdominal circumference, body mass index, and fat folds were the main outcome measures. RESULTS: Anthropometrical measurements showed no significant differences between ICSI and IVF children and controls in either cohort. However, singleton ICSI girls [3.4 (0.6) kg, P = 0.008] had a slightly lower birth weight than IVF [3.5 (0.5) kg] and NC girls [3.5 (0.5) kg]. Birth weights of singleton boys [3.6 (0.5) kg], twin boys [2.6 (0.6) kg], and twin girls [2.4 (0.5) kg] did not differ between types of conception. In the infant cohort in 3-month-old singletons, serum IGF-I was lower in ICSI [78 (26) ng/ml] than NC boys [94 (27) ng/ml, P < 0.001] and IVF [74 (34) ng/ml], compared with NC girls [93 (43) ng/ml, P = 0.011]. ICSI children were also smaller than their target height (sd score) at 3 yr of age [mean -0.91 (1.2)], compared with NC children [-0.61 (0.9), P = 0.033]. In the child cohort, target height attainment (sd score) and growth factors did not differ among the three groups. CONCLUSIONS: The overall growth pattern of ICSI and IVF children in both cohorts was normal. Our findings of subtle differences in target height attainment and serum IGF-I levels between infants born after assisted reproduction techniques and controls may not be clinically significant. However, these observations indicate that further systematic follow-up of growth and puberty in these children is needed.

Body Height↗