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[Multiples births: a continuing problem with assisted reproductive techniques].

Assisted reproductive techniques (ART) such as in vitro fertilisation (IVF), ovulation induction and superovulation followed by insemination have caused a sharp increase in multiple birth prevalence rates. The perinatal morbidity of multiple birth infants is high because of the high incidence of premature birth. The social and psychological problems of multiple birth families are also considerable. In 1990 high-order multiple births were mainly the result of IVF. Although the number of IVF treatments has increased more than the number of other ART treatments, nowadays high-order multiple births are predominantly caused by superovulation. Since 1990 the number of high-order multiple births has stabilised, but the recent sharp increase in ART twins results in a further rise in births of severely preterm ART infants. More restraint should be practised in superovulation treatments to bring down the number of (high-order) multiple births.

Adult↗

Encouraging results despite complexity of multidisciplinary care of HIV-infected women using assisted reproduction techniques.

BACKGROUND: Assisted reproduction technologies can treat infertility for human immunodeficiency virus (HIV) seropositive women. We assessed the efficacy of these techniques in the results and difficulties encountered while conducting our assisted reproduction programme for 49 couples in which at least the woman had HIV infection that was currently under control. METHODS: Treatments included intrauterine insemination (IUI), IVF and ICSI, with ovarian stimulation. Embryos were transferred on day 3 after oocyte retrieval. An elective single transfer was performed, except for patients aged > or = 40 years. RESULTS: The median age of the women was 36 years. Ten IUI, nine IVF, 53 ICSI and 10 frozen-thawed embryo transfers have been performed. No pregnancy occurred following the IUI trials but for the couples with IVF and ICSI attempts the clinical pregnancy rate per embryo transfer was 23.9%. Eight babies have been born leading to a 22.2% take home baby rate per treated couple. Contamination was not observed in any newborn. CONCLUSIONS: Assisted reproduction technologies and particularly ICSI can provide HIV seropositive women with a safe means of mothering children. Results are encouraging when considering the age of the patients and a preferential single embryo transfer.

Adult↗

Down's syndrome screening in pregnancies after assisted reproductive techniques: an update.

Assisted reproductive techniques have increased the number of pregnant women beyond the age of 35 years and the incidence of multiple pregnancies. Various non-invasive screening methods for Down's syndrome were introduced in clinical practice during the past two decades. Specific problems were encountered when these methods were applied for pregnancies achieved by assisted reproduction treatment and the aim of this review is to explore these issues and propose an adjusted methodological approach for this highly selected population. Overall, more women with assisted reproduction singleton pregnancies are found to be false-positive for Down's syndrome. This is because standard screening algorithms include maternal age. In addition, mid-trimester maternal serum screening is associated with a higher false-positive rate. This is due to changes in the feto-placental endocrinological metabolism in pregnancies achieved by assisted reproduction treatment. Ultrasound screening of Down's syndrome by means of nuchal translucency (NT) measurements at 10-14 weeks is associated with a lower false-positive rate than mid-trimester serum screening. The lowest false-positive rates reported in singleton pregnancies are observed when serum and nuchal translucency screening are combined at 10-14 weeks. In multiple pregnancies, mid-trimester maternal serum screening is of limited clinical value. Nuchal translucency measurement is among the best available and is the most efficient screening method for multiple pregnancies. This sonographical method for screening enables specific identification of those fetuses at high risk of Down's syndrome and other anomalies, and thus contributes to a better outcome. Therefore, it should be systematically performed before any fetal reduction in high-order multiple pregnancies is planned.

Chorionic Gonadotropin↗

Transmission risk of hepatitis C virus in assisted reproductive techniques.

Medical assistance for procreation in a couple where one or both parents has hepatitis C viral infection (HCV) raises the issue of the transmission of the infection to the baby and/or of possible contamination of both the technicians and the gametes or embryos from virus-free parents in the laboratory. It becomes essential to assess transmission risk in assisted reproductive techniques in order to define clearly the management of couples according to their viral status. To define the HCV transmissibility risk in assisted reproduction related to the presence of virus in semen from infected infertile men, HCV RNA detection was performed in sera, and semen and sperm fractions obtained after Percoll gradient centrifugation. HCV RNA was detected in 5% (2/39) of the semen samples tested: in the raw semen, in the seminal fluid and in the cell pellet but never after Percoll selection. According to these results, we suggest a strategy for HCV-infected infertile men who need assistance for procreation.

Adult↗

A short review of ovarian stimulation in assisted reproductive techniques.

Ovarian stimulation during assisted human reproduction is currently a standard procedure in assisted reproductive techniques (ART). Its objective is to stimulate the growth of several follicles by injections of FSH-containing compounds, most recently recombinant FSH (rFSH). An injection of human chorionic gonadotrophin (HCG), or a luteinizing hormone-releasing hormone agonist to discharge pituitary LH is then given to invoke follicle and oocyte maturation. Various other medications are also used in addition to specific drugs such as human menopausal gonadotrophin, rFSH, HCG and rLH. Non-specific drugs include clomiphene citrate, other anti-oestrogens, bromoergocryptine, and gonadotrophin-releasing hormone (GnRH) agonists and antagonists. Numerous protocols have been utilized with these agents, the most common being clomiphene citrate and various regimens of gonadotrophins, including step-up, step-down and continuous. The regimens are used with or without GnRH agonists, and with or without GnRH antagonists. In this brief review, the advantages and disadvantages of each protocol are presented.

Clomiphene↗

Assisted reproductive techniques--promises and problems.

Assisted reproductive techniques (ART) are procedures in which the oocyte is handled before replacement, either as an oocyte or embryo. The current success rates and pregnancy outcomes of in-vitro fertilisation (IVF), gamete intra-fallopian transfer (GIFT), zygote intra-fallopian transfer (ZIFT), intra-cytoplasmic sperm injection (ICSI), donor oocyte and frozen embryo programmes are reviewed. Some problems associated with assisted reproductive procedures are also discussed.

Female↗

[Andrologic indications for assisted reproduction techniques. When can increased fertilization rates by assisted reproduction be expected?].

Basics: When the cause of a sterile marriage must be assumed to lie with the husband, attempts are often made to resolve the problem by applying the techniques of assisted reproduction, viz insemination and in vitro fertilization (IVF). In such a case, this is the treatment of the wife, who may herself be completely healthy. Major points: In the case of oligoasthenoteratozoospermia (OAT) syndrome, the various techniques available are unable to decisively increase the conception rate. In particular, all IVF working groups are agreed that successes are greatly reduced in the case of inferior sperm quality, as compared with other indications. The "poorer" the original findings, the lower are the fertilization rates. The costs of IVF of about DM 6,000 per cycle mean that, with a success rate of some 8%, the overall cost for each pregnancy is about DM 72,000. This fact tends not to receive sufficient mention in discussions with the married couple. So far, it has not been possible to predict the success rate of an IVF on the basis of an examination of the ejaculate with any degree of accuracy with the aid of the parameters sperm cell density, motility and morphology. Nor do biological tests or an investigation of acrosome function help improve the situation. Even the direct observation of the fertilization of a human ovum, is of questionable value.(ABSTRACT TRUNCATED AT 250 WORDS)

Fertilization in Vitro↗

Using willingness to pay to assess the benefits of assisted reproductive techniques.

Current economic evaluations of Assisted Reproductive Techniques (ARTs) are criticized for assuming that the only factor important to users is whether they leave the service with a child. Such an approach ignores, first, outcomes beyond some narrow medical definition of success, second, the majority of users who leave the service childless and, third, the actual process of treatment. The aim of this study was to establish the importance of factors beyond some medical definition of success in the provision of ARTs, using the economic instrument of willingness to pay (WTP). The results suggest that there is some value in going through the service, even if the couple leaves it childless. It is concluded that the WTP technique is potentially useful in evaluating ARTs but further studies need to be undertaken to assess its reliability and validity.

Adult↗

Risks and complications in assisted reproduction techniques: Report of an ESHRE consensus meeting.

Assisted reproduction technique (ART) is an efficacious treatment in subfertile couples. So far little attention has been paid to the safety of ART, i.e. to its adverse events and complications. The consensus meeting on Risks and Complications in ART held in Maastricht in May 2002 focused on four topics: multiple pregnancies, long-term effects of ART on women, effects of ART on offspring, and morbidity/mortality registries.

Breast Neoplasms↗

Assisted reproduction techniques for HIV serodiscordant couples: 18 months of experience.

BACKGROUND: Assisted reproduction techniques can minimize the risk of infection and treat possible sterility associated with serodiscordant couples. METHODS: We assessed the efficacy of these techniques in 57 couples in which at least one partner had human immunodeficiency virus (HIV-1) infection that was currently under control (47 men and 10 women). The semen of seropositive men was prepared and tested for viruses. Assisted reproduction techniques included intrauterine insemination (IUI), IVF and especially ICSI, with ovarian stimulation that used a long agonist protocol and recombinant FSH. Embryos were transferred on day 3 after oocyte retrieval. RESULTS: For couples with seropositive men, five IUI and 49 IVF or ICSI attempts were perfomed, whilst for seropositive women these numbers were three IUI and 12 IVF or ICSI. No pregnancy occurred following the eight IUI trials. Seroconversion was not observed in any partners of seropositive men. Efficacy of treatment for these couples with ICSI was good, the clinical pregnancy rate per embryo transfer was 48.8%. The results for seropositive women were disappointing, with a clinical pregnancy rate per embryo transfer of 9.1%. Fourteen babies from 47 treated couples have so far been born and no pregnancies from IUI. CONCLUSIONS: Assisted reproduction techniques and particularly ICSI provide HIV-1-seropositive men with a safe and highly effective means of fathering children. These techniques may be less effective for seropositive women.

Acquired Immunodeficiency Syndrome↗

Cloning and assisted reproductive techniques: influence on early development and adult phenotype.

Over the past 40 years, our increased understanding and development of cell and molecular biology has allowed even greater advances in reproductive biology. This is most evident by the development of various aspects of assisted reproductive techniques (ART), generation of transgenic animals, and most recently generation of mammals through somatic cell cloning. To date, cloning from adult somatic cells has been successful in at least 10 mammalian species. Although generating viable cloned mammals from adult cells is technically feasible and the list of successes will only continue to grow with time, prenatal and perinatal mortality is high and live cloned offspring have not been without health problems. The success of many of the proposed applications of the cloning technique obviously depends upon the health and survival of founder animals generated by nuclear transfer. This article summarizes the health consequences of cloning in mice, and discusses possible mechanisms through which these conditions may arise. In addition, we discuss the effects of ART in animal models and in humans. ART also involves some of the same procedures used in cloning, and there are reports that offspring generated by ART sometimes display aberrant phenotypes as well. It is important to point out that although these techniques do sometimes produce abnormalities, the majority of offspring are born apparently normal and survive to adulthood. Additionally, we must emphasize that the effects of ART and cloning observed in animal models do not necessarily indicate that they will occur in humans. In this article, we review studies examining the phenotype of animals generated by cloning and various ART, and discuss clinical implications of these findings.

Animals↗

Relationship between pre-embryo pronuclear morphology (zygote score) and standard day 2 or 3 embryo morphology with regard to assisted reproductive technique outcomes.

OBJECTIVE: To test the hypothesis that pregnancy rates are low if grade Z1 pre-embryos are not available for transfer and to determine if pronuclear morphology is a better predictor of pregnancy than traditional embryo morphology. DESIGN: Prospective clinical study. SETTING: Academic human reproduction laboratory. PATIENT(S): One hundred couples undergoing IVF with conventional insemination or ICSI. INTERVENTION(S): Embryo quality was assessed using both pre-embryo pronuclear morphology (zygote scoring or Z-scoring) at the time of fertilization evaluation and standard day 2 and day 3 embryo morphology (number of blastomeres and grading based on degree of fragmentation and blastomere size). MAIN OUTCOME MEASURE(S): We tested two decision models, one based on Z-scores and another on morphology, to determine which grading system better predicted pregnancy outcomes in assisted reproductive technique. Zygote score and embryo morphology were measured for all embryos and the transferred embryo pool. Implantation and pregnancy rates resulting from the embryo transfers of all cycles were calculated. RESULT(S): The Z-score distribution of 552 embryos was 27% Z1, 8% Z2, 50% Z3, and 15% Z4. Z1 and Z3 embryos had significantly (P approximately .03) higher quality over Z2 and Z4 embryos. Using the Z-score decision model with Z1 embryos having highest priority for transfer, pregnancy rates were similar between Z1 and Z3 embryos. Using embryo morphology as a decision model, pregnancy rates were highest in transfers containing one or two "best"-quality embryos. CONCLUSION(S): Z1 and Z3 embryos had similar morphology and pregnancy rates. The decision model based on the Z-score model was not better than standard embryo morphology in predicting pregnancy outcome.

Adult↗

[Perinatal outcome of twin pregnancies conceived by assisted reproductive techniques and those conceived spontaneously].

OBJECTIVE: To investigate perinatal outcomes of twin pregnancies conceived by assisted reproductive techniques and those conceived spontaneously. METHODS: The pregnant complications, delivery situation and neonatal outcomes of 104 twin pregnancies conceived by assisted reproductive techniques were compared to 173 spontaneous ones. RESULTS: (1) The women of twin pregnancies conceived by assisted reproductive techniques were (31.2 +/- 3.7) years old while the spontaneous ones were (27.8 +/- 3.5) years old. There was significant difference between two groups (P < 0.05). (2) There were also significant differences in the incidence of premature delivery and gestational diabetes mellitus or impaired glucose tolerance(P < 0.01) between two groups. There were 70 cases (67.3%) premature delivery in assisted reproduction group, while 78 cases (45.1%) in spontaneous group. There were 16 cases (15.4%) gestational diabetes mellitus or impaired glucose tolerance in assisted reproduction group, while 4 cases (2.3%) in spontaneous group. (3) Cesarean sections were more frequently performed in assisted reproduction group (79 cases, 76.0%) than in spontaneous group (113 cases 65.3%). (4) There were no statistically significant differences in perinatal deaths, congenital malformations, neonatal asphyxia between two groups (P < 0.05). CONCLUSION: The women of twin pregnancies conceived by assisted reproductive techniques were older than those conceived spontaneously. The incidence of premature delivery, gestational diabetes mellitus or impaired glucose tolerance and cesarean section were higher in assisted reproduction group. However, no statistically significant differences in perinatal morbidity were found between the two groups.

Adult↗

Pregnancy and child outcome after assisted reproduction techniques.

The introduction and widespread application of assisted reproduction techniques have raised major concern about the outcome of resulting pregnancies, as well as about the offspring's health. It seems that pregnancies achieved after standard in-vitro fertilization (IVF) bear an increased risk for prematurity and low birth weight. On the other hand, pregnancy outcome of singletons achieved after intracytoplasmic sperm injection (ICSI) and after the transfer of frozen-thawed embryos is similar to that of spontaneously conceived singletons, and pregnancy complications are related only to gestation multiplicity. The incidence of congenital and chromosomal anomalies after standard IVF seems to be similar to that expected in the general population. The prevalence of congenital malformations does not seem to be higher after ICSI. On the other hand, there is a slightly increased risk for transmission of chromosomal aberrations of paternal origin and a higher risk of de novo, mainly sex-chromosomal aberrations. Postnatal growth and development of children born after standard IVF and cryopreservation seem to be within the normal ranges. Growth of ICSI children is also normal while their mental development needs further investigation. Family functioning in assisted reproduction families is better.

Child Development↗

[Are French results in assisted reproductive techniques so bad?].

OBJECTIVE: Comparative analysis of French results in Assisted Reproductive Techniques (ART) versus those from other European countries and the United States. POPULATION AND METHODS: The study was achieved by using the officially available data. The analysis was faced with a lot of difficulties in relation with the various methods of collecting data in the different countries. RESULTS: Nevertheless, it appears clearly that French results are among the lowest in Europe with a 22% rate for pregnancy per ovum pick-up with IVF and 23.4% with ICSI, when most of the other countries report rates that are close to or over 30%. Neither the patients' pick-up recruitment nor specific practices of ART can explain this difference that certainly comes from a deficient quality of the French IVF centres. DISCUSSION AND CONCLUSION: We think that four main end-points can explain this situation: the lack of financial support, the lack of human force, the lack of transparency and finally the opposition between clinician and biologist that has blocked the set-up of integrated ART centres, and probably a poor quality culture.

Adult↗

Psychological evaluation test after the use of assisted reproduction techniques.

PURPOSE: The emotional changes provoked by the use of assisted reproduction techniques (ART) may trigger important psychological reactions. The objective of the present study was to develop a psychological evaluation test (PET-ART) in order to identify the occurrence of psychological problems and to facilitate their treatment. METHODS: A total of 128 women were submitted to PET-ART of the Center for Human Reproduction, "Sinhá Junqueira" Maternity Foundation, after application of IVF/ICSI program at least once. The causes of infertility were male-related in 45% of cases, female-related in 48%, and both male- and female-related in 7%. Infertility was primary in 79% of cases and secondary in 21%. The mean age of the women was 34.5 +/- 5.2 years and the mean age of the men was 37.9 +/- 6.8 years. The PET-ART was evaluated using a questionnaire with 15 questions selected in order to detect emotional reactions caused by infertility. The responses were assigned four grades with respect to intensity (1 = mild intensity; 2 = medium intensity; 3 = high intensity; and 4 = maximum or unbearable intensity). The sum of the responses corresponded to PET-ART score ranging from 15 to 60 points. The reliability of the questionnaire was evaluated by the alpha coefficient of Cronbach. RESULTS: The PET-ART identified five questions receiving 50% or more responses of the high/maximum intensity type (sum of the percentages of responses with a score of 3 and 4). The questions were the following: 1--The waiting time before being submitted to a pregnancy test (82.8% of the patients); 2--A negative result of the pregnancy test (77.3% of the patients); 3--The degree of anxiety in a new attempt to obtain pregnancy (76.5% of the patients); 4--Finding the money necessary for the repetition of the IVF/ICSI techniques (66.4% of the patients); 5--The possibility of collecting few eggs, or of forming or not an embryo in the laboratory is an expectation that makes me anxious (57.8% of the patients). The mean PET-ART was 33 +/- 6. The alpha coefficient of Cronbach was 0.757. CONCLUSIONS: The PET-ART was an efficient tool for the identification of women with emotional changes provoked by the application of ART and for the planning of their treatment. However, a general psychological approach was developed for each emotional factor regardless of PET-ART.

Adult↗

Heterotopic pregnancies after controlled ovarian hyperstimulation and assisted reproductive techniques.

Eight cases of heterotopic pregnancy following assisted reproductive techniques (ART) were reviewed. One cervical, three cornual and four tubal pregnancies were combined with intrauterine pregnancies. The cervical ectopy was successfully treated with a local injection of potassium chloride (KCl) into the gestational sac. A viable baby was produced from the intrauterine gestation. Cornual metroplasties were performed on two ruptured and one unruptured cornual heterotopic pregnancies. One of these three cases was maintained till term. All four tubal heterotopic pregnancies were aborted. Widespread application of ART in recent years has meant that heterotopic pregnancies are no longer a rarity. Both physicians and patients should be made aware that the existence of an intrauterine gestation does not preclude the risk of nidation of other fetuses in ectopic sites. The authors recommend that detailed ultrasound studies, preferably via the vaginal route, should be performed on patients in ART programs. During the examination, the adnexae should be carefully evaluated, even if an intrauterine gestational sac is already present. If a heterotopic pregnancy is diagnosed, the appropriate treatment depends on the location of ectopic pregnancy. Local injection with KCl or methotrexate is effective in certain types of cervical or cornual ectopic pregnancy, as it may allow the conservation of the intrauterine pregnancy.

Adult↗

Risk of cesarean section in singleton pregnancies after assisted reproductive techniques.

OBJECTIVE: To evaluate the perinatal outcome of singleton pregnancies after assisted reproductive techniques in comparison with that in matched controls from spontaneous pregnancies. STUDY DESIGN: A total of 11,776 deliveries from January 1, 1995, to May 31, 2001, were subjected to retrospective analysis. Data on 259 neonates from singleton pregnancies after ovulation induction (n = 85, 32.8%), intrauterine insemination (n = 17, 6.6%) or in vitro fertilization (n = 157, 60.6%) were evaluated. The pregnancy outcome was compared with that for controls (n = 518) matched for age, gravidity and parity after spontaneous pregnancies. RESULTS: Cesarean section was significantly more frequent in the study group than in the control group (42.1% vs. 27.6%, P < .001, odds ratio [OR] 1.91, 95% confidence interval [CI] 1.39-2.61). The prevalence of preterm deliveries was not significantly higher (P = .40, OR 1.23, 95% CI .78-1.95) in the study group as compared with the controls (12.7% vs. 10.6%). There was no significant difference in intrauterine growth retardation between the two groups (9.3% vs. 6.2%, P = .14, OR 1.55, 95% CI .89-2.69). CONCLUSION: Singleton pregnancies after assisted reproductive techniques are associated with an increased rate of cesarean section, whereas neonatal outcome is not influenced.

Adult↗